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This report is written by MaltSci based on the latest literature and research findings

What is the role of B cells in immune function? ​

Abstract ​

B cells are integral components of the adaptive immune system, primarily known for their ability to produce antibodies that neutralize pathogens and facilitate their clearance. This review provides a comprehensive overview of the roles of B cells in immune function, emphasizing their development, activation mechanisms, and diverse contributions to both protective immunity and immune regulation. B cells originate from hematopoietic stem cells in the bone marrow, where they undergo a rigorous selection process to ensure effective antigen recognition while avoiding autoimmunity. Key transcription factors and signaling pathways govern their maturation and differentiation into functional subsets, including memory B cells and plasma cells. The interaction between B cells and T helper cells is critical for optimal B cell activation, leading to the production of high-affinity antibodies and the formation of immunological memory. Memory B cells are essential for long-term immunity, enabling rapid responses upon re-exposure to pathogens. Additionally, regulatory B cells have emerged as key players in modulating immune responses and maintaining tolerance, with implications for the treatment of autoimmune diseases. Understanding the multifaceted roles of B cells is crucial for developing targeted immunotherapies and enhancing vaccine efficacy, thereby advancing our ability to combat infectious diseases and manage immune-mediated disorders.

Outline ​

This report will discuss the following questions.

  • 1 Introduction
  • 2 Development and Differentiation of B Cells
    • 2.1 Origin and maturation in the bone marrow
    • 2.2 Selection processes and mechanisms
  • 3 Mechanisms of B Cell Activation
    • 3.1 Antigen recognition and signaling pathways
    • 3.2 Role of T helper cells in B cell activation
  • 4 Antibody Production and Function
    • 4.1 Types of antibodies and their roles
    • 4.2 Mechanisms of antibody-mediated immunity
  • 5 Memory B Cells and Immune Memory
    • 5.1 Formation and maintenance of memory B cells
    • 5.2 Role in vaccination and long-term immunity
  • 6 Regulatory B Cells and Immune Regulation
    • 6.1 Function and mechanisms of regulatory B cells
    • 6.2 Implications in autoimmunity and tolerance
  • 7 Summary

1 Introduction ​

B cells are integral components of the adaptive immune system, playing a crucial role in the body's defense against pathogens. These lymphocytes are primarily known for their ability to produce antibodies, which are essential for neutralizing pathogens and marking them for destruction by other immune cells. The significance of B cells extends beyond antibody production; they are pivotal in the development of immunological memory, allowing for a more rapid and effective response upon subsequent exposures to the same antigen. The multifaceted roles of B cells have been increasingly recognized in recent years, particularly in relation to their involvement in various immune responses, autoimmune diseases, and malignancies. This review aims to provide a comprehensive overview of the functions of B cells in immune function, highlighting their development, mechanisms of action, and implications in health and disease.

The development and differentiation of B cells occur primarily in the bone marrow, where they undergo a rigorous selection process to ensure the effective recognition and response to a diverse array of antigens while avoiding autoimmunity. This process involves the generation of various B cell subsets, each with distinct functions that contribute to immune regulation and homeostasis [1][2]. Recent research has highlighted the heterogeneity of B cell populations, including memory B cells and regulatory B cells, which play crucial roles in maintaining immune tolerance and modulating immune responses [3][4]. Understanding the development and functional diversity of B cells is vital for elucidating their roles in both protective immunity and pathogenic autoimmunity [5].

The mechanisms by which B cells are activated are complex and involve antigen recognition and signaling pathways, often in collaboration with T helper cells [6]. The interaction between B cells and T cells is critical for the generation of high-affinity antibodies and the formation of immunological memory [7]. Moreover, the production of different types of antibodies, such as IgM and IgG, is tailored to respond effectively to specific pathogens [1]. Understanding these mechanisms is essential for developing targeted immunotherapies that can enhance B cell function in various diseases.

B cells also contribute significantly to the formation and maintenance of memory B cells, which are crucial for long-term immunity [8]. The role of memory B cells in vaccination strategies is particularly noteworthy, as they enable a rapid and robust response upon re-exposure to pathogens [9]. Additionally, the dysregulation of B cell function is implicated in a range of diseases, including autoimmune disorders and cancers, underscoring the importance of understanding their role in immune function [6][10].

Regulatory B cells, a specialized subset of B cells, have garnered attention for their ability to modulate immune responses and maintain tolerance [3][11]. These cells produce anti-inflammatory cytokines, such as IL-10, which can suppress pro-inflammatory responses and play a protective role in various diseases [4]. The dysregulation of regulatory B cells is associated with autoimmune conditions, highlighting their potential as therapeutic targets [7].

In summary, this review will explore the following key areas: the development and differentiation of B cells, the mechanisms of B cell activation, the diverse roles of antibodies in immune function, the significance of memory B cells in long-term immunity, and the regulatory functions of B cells in maintaining immune homeostasis. By integrating findings from recent research, we aim to provide a comprehensive understanding of the critical roles that B cells play in immune function and their implications in health and disease. This knowledge is essential for developing novel therapeutic strategies aimed at modulating B cell responses in various clinical contexts.

2 Development and Differentiation of B Cells ​

2.1 Origin and maturation in the bone marrow ​

B cells, a crucial component of the adaptive immune system, originate from hematopoietic stem cells (HSCs) in the bone marrow and undergo a series of developmental stages that culminate in their maturation into functional immune cells. This process begins with the differentiation of HSCs into pro-B cells, which subsequently progress through several stages characterized by specific surface markers and functional capabilities.

In the bone marrow, B cell development is tightly regulated by various transcription factors and signaling pathways. Key transcription factors such as E2A, EBF1, and Pax5 are essential for B lineage specification and maintenance during the early stages of differentiation. The process of B cell maturation involves the rearrangement of immunoglobulin genes, allowing the formation of a functional B cell receptor (BCR). At the pro-B cell stage, the immunoglobulin heavy chain gene undergoes rearrangement, followed by further development at the large pre-B stage where cells that successfully express a functional heavy chain are selected for expansion in response to signals from interleukin-7 (IL-7) and the pre-BCR [12].

Once the BCR is fully formed and expressed on the surface of immature B cells, these cells migrate to peripheral lymphoid tissues, such as the spleen, where they further differentiate into either memory B cells or plasma cells. This transition is crucial for the ability of B cells to respond to antigens effectively. Memory B cells retain the ability to mount a rapid and robust immune response upon re-exposure to the same antigen, while plasma cells are responsible for the production and secretion of antibodies [13].

B cells also play a vital role in maintaining immune tolerance and preventing autoimmunity. During their development, B cells that express receptors recognizing self-antigens are typically eliminated through mechanisms that promote central tolerance. This process ensures that the B cell repertoire is skewed towards recognizing foreign antigens while minimizing the risk of autoimmunity [14].

The interaction between B cells and their microenvironment within the bone marrow is also significant. Mesenchymal stem cells in the bone marrow niche provide essential support for B cell differentiation and maintenance. They can modulate B cell proliferation and differentiation, influencing the overall immune response [15]. Additionally, B cells contribute to bone biology and the interplay between the immune system and skeletal system, demonstrating their multifaceted roles beyond antibody production [16].

In summary, B cells are integral to the adaptive immune response, with their development and maturation occurring primarily in the bone marrow. They transition from progenitor cells to mature B cells capable of producing antibodies, maintaining immune memory, and regulating immune tolerance, thereby ensuring a balanced and effective immune response.

2.2 Selection processes and mechanisms ​

B cells play a pivotal role in the immune system, primarily through their ability to produce antibodies, but their functions extend beyond this traditional view. The development and differentiation of B cells involve complex selection processes that ensure the generation of a diverse and functional B cell repertoire capable of responding to a wide range of antigens while maintaining self-tolerance.

The journey of B cell development begins in the bone marrow, where progenitor cells undergo several stages of maturation. During this process, B cells are subjected to a series of selection mechanisms that ensure the functional integrity of the immune response. Central to this is the process of negative selection, which eliminates B cells that strongly recognize self-antigens, thus preventing autoimmunity. This is achieved through receptor editing, where B cells can alter their antigen receptors (BCRs) to avoid self-reactivity, a critical mechanism highlighted by Renaudineau et al. (2004) in their exploration of dysfunctional B cells in systemic lupus erythematosus [5].

Upon successful maturation, B cells migrate to peripheral lymphoid organs, where they encounter antigens. The activation of naïve B cells occurs primarily in response to T cell help, particularly in germinal centers, where they undergo affinity maturation and class switching. This process is crucial for producing high-affinity antibodies tailored to effectively neutralize pathogens. The dynamics of B cell activation and differentiation are further regulated by various signals from the microenvironment, including cytokines and interactions with T cells, as discussed by Tangye et al. (2024) [8].

Moreover, B cells can differentiate into memory B cells and plasma cells. Memory B cells provide long-lasting immunity by retaining the ability to respond rapidly upon re-exposure to the same antigen, while plasma cells are specialized for high-level antibody production. The differentiation into these subsets is influenced by the signals received during activation, including cytokines such as IL-10, which plays a role in regulating B cell functions and promoting tolerance [3].

In summary, the role of B cells in immune function encompasses a sophisticated network of developmental and selection processes. These mechanisms ensure the generation of a diverse B cell population capable of responding to pathogens while preventing autoimmunity, highlighting the importance of both positive and negative selection in maintaining immune homeostasis. The intricate interplay of signals during B cell maturation and differentiation underscores the complexity of their contributions to immune responses and tolerance.

3 Mechanisms of B Cell Activation ​

3.1 Antigen recognition and signaling pathways ​

B cells play a pivotal role in the immune system, primarily responsible for the production of antibodies that provide protection against pathogens. Their activation and subsequent differentiation into memory B cells and antibody-secreting plasma cells are essential for establishing long-lived humoral immunity. The process of B cell activation is initiated when B cells recognize specific antigens through their B cell receptors (BCRs). This recognition triggers a series of signaling cascades that lead to various cellular responses, including proliferation, differentiation, and antibody production.

The BCR is a transmembrane protein that recognizes specific antigens, and its engagement with these antigens initiates intracellular signaling pathways crucial for B cell activation. Upon antigen binding, BCR microclusters form, which serve as sites for active signaling through the recruitment of intracellular signaling molecules and adaptors. This process is further enhanced by the spreading of B cells in a CD19-dependent manner, ultimately leading to the formation of a mature immunological synapse. This synapse is essential for antigen internalization and subsequent presentation to helper T cells, which is critical for maximal B cell activation [17].

In addition to BCR signaling, B cells also express Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs). The dual engagement of BCRs and TLRs can fine-tune B cell responses, linking innate and adaptive immune pathways. This integration of signaling from both BCRs and TLRs enhances B cell activation and antibody production, demonstrating the complexity of the immune response [18].

Furthermore, B cells are capable of presenting antigens to T cells, acting as professional antigen-presenting cells (APCs). This antigen presentation can occur through both antigen-specific (BCR-dependent) and non-specific (BCR-independent) mechanisms, allowing B cells to influence T cell activation and the overall immune response [19].

The cytokine environment also plays a crucial role in B cell activation and function. Cytokines can modulate the signaling pathways involved in B cell differentiation and antibody production. Recent studies have identified specific cytokine signaling pathways that are essential for generating and maintaining memory B cells and plasma cells, highlighting the importance of the microenvironment in shaping B cell responses [20].

Overall, the activation of B cells involves a complex interplay of antigen recognition, signaling pathways, and interactions with other immune cells. These processes ensure that B cells can effectively respond to infections, produce high-affinity antibodies, and maintain immunological memory, while also preventing dysregulation that could lead to autoimmune diseases or allergies [8].

3.2 Role of T helper cells in B cell activation ​

B cells play a multifaceted role in immune function, primarily recognized for their contributions to humoral immunity through antibody production. They also serve as crucial antigen-presenting cells (APCs) and have the capacity to modulate T cell responses. The mechanisms of B cell activation and their interactions with T helper cells are vital for understanding their function in the immune system.

B cells are involved in both antigen-specific and non-specific mechanisms of antigen presentation. Antigen presentation through B cells can occur via B cell receptor (BCR) dependent pathways, where specific antigens are recognized and internalized, processed, and presented on major histocompatibility complex (MHC) class II molecules to T cells. This interaction is essential for T cell activation and differentiation. Additionally, B cells can engage in antigen presentation through BCR independent mechanisms, influenced by various intrinsic and extrinsic factors, such as cytokines and other signals from the microenvironment [19].

The interaction between B cells and T helper cells is critical for effective immune responses. T helper cells, particularly T follicular helper (Tfh) cells, provide necessary signals for B cell activation, maturation, and differentiation. This process involves direct cell-cell contact and the secretion of lymphokines, which act as growth and differentiation factors for B cells. Tfh cells enhance B cell responses through two components: lymphokines that promote B cell growth and differentiation, and contact-dependent signals that are crucial for full B cell activation [21].

In addition to their traditional roles in antibody production, B cells can also down-regulate immune responses, showcasing a dual role in immunity. Activated B cells, particularly those expressing CD25, can induce T cell anergy and apoptosis under certain conditions, highlighting their regulatory functions in immune responses [22]. Furthermore, the activation of B cells can be influenced by external cues, such as surface topology and biochemical signaling, which can modulate their functions in immunotherapy contexts [23].

The necessity of T helper cells in B cell activation is further emphasized in studies demonstrating that B cells are crucial for generating memory T cell responses. For instance, the absence of B cells impairs the generation of memory precursor effector cells (MPECs) following vaccination, indicating that B cells are integral in shaping long-term T cell immunity [24]. This interdependence illustrates the collaborative nature of B and T cell interactions in establishing effective immune responses.

Overall, B cells are essential for orchestrating both humoral and cellular immunity through their roles as APCs, producers of antibodies, and modulators of T cell activity. Their activation is intricately linked to T helper cells, which provide critical signals that influence B cell fate and function, thereby shaping the overall immune response. Understanding these mechanisms is crucial for developing targeted immunotherapies and enhancing vaccine efficacy.

4 Antibody Production and Function ​

4.1 Types of antibodies and their roles ​

B cells play a crucial role in the immune system primarily through their ability to produce antibodies, which are essential for humoral immunity. These antibodies are proteins that recognize and bind to specific antigens, which can be pathogens such as bacteria and viruses, facilitating their neutralization and clearance from the body. The process of antibody production is complex and involves several key steps, including the activation of B cells, clonal expansion, and differentiation into plasma cells that secrete antibodies.

There are several types of antibodies, also known as immunoglobulins (Igs), each with distinct roles in immune responses:

  1. IgM: This is the first antibody produced in response to an infection. It is primarily found in the bloodstream and is effective in forming complexes with antigens, leading to their agglutination and subsequent clearance by phagocytic cells. IgM is particularly important in the early stages of immune response.

  2. IgG: This is the most abundant antibody in serum and plays a vital role in long-term immunity. IgG can cross the placenta, providing passive immunity to the fetus. It is highly effective in opsonization, which enhances phagocytosis, and neutralizes toxins and viruses. IgG also activates the complement system, which helps in lysing pathogens.

  3. IgA: Predominantly found in mucosal areas such as the gut, respiratory tract, and secretions like saliva and breast milk, IgA plays a critical role in mucosal immunity. It prevents the adherence of pathogens to epithelial cells and neutralizes toxins, thus protecting mucosal surfaces from infections.

  4. IgE: This antibody is primarily involved in allergic reactions and responses to parasitic infections. IgE binds to allergens and triggers histamine release from mast cells and basophils, leading to allergic symptoms. It is also crucial in mediating immune responses against helminthic infections.

  5. IgD: Although its exact function is less understood, IgD is primarily found on the surface of immature B cells and is believed to play a role in B cell activation and differentiation.

B cells not only produce antibodies but also act as antigen-presenting cells (APCs). They can process and present antigens to T cells, thus facilitating a coordinated immune response. This antigen presentation is crucial for the activation of T cells, which further enhances the adaptive immune response [19].

Moreover, B cells are involved in the regulation of immune responses through the secretion of various cytokines. For instance, they can produce immunosuppressive cytokines such as interleukin-10 (IL-10), which helps maintain immune tolerance and prevent excessive inflammation [1].

In summary, B cells are integral to immune function through their diverse roles in antibody production, antigen presentation, and cytokine secretion, contributing to both protective and regulatory aspects of the immune response. Their ability to produce different types of antibodies enables the immune system to effectively combat a wide range of pathogens and maintain homeostasis.

4.2 Mechanisms of antibody-mediated immunity ​

B cells play a pivotal role in the immune system, primarily through their ability to produce antibodies, which are crucial for the defense against pathogens. The mechanism of antibody-mediated immunity involves several key processes that are essential for effective immune responses.

Firstly, B cells are responsible for the generation of antibodies that specifically recognize and bind to antigens, which are foreign substances that trigger an immune response. Upon encountering an antigen, B cells undergo a process known as clonal expansion, where they proliferate and differentiate into two main types of cells: plasma cells and memory B cells. Plasma cells are specialized for the production and secretion of large quantities of antibodies, while memory B cells persist long-term and provide a rapid and robust response upon re-exposure to the same antigen [8].

The antibodies produced by B cells can neutralize pathogens directly by binding to them and preventing their entry into host cells. Additionally, antibodies can opsonize pathogens, marking them for destruction by phagocytic cells such as macrophages and neutrophils. This opsonization enhances the efficiency of phagocytosis, facilitating the clearance of pathogens from the body [25].

Furthermore, B cells also contribute to antibody-mediated immunity through their role as antigen-presenting cells (APCs). They can process and present antigens to T cells, thereby facilitating T cell activation and the subsequent adaptive immune response. This interaction is crucial for the generation of a coordinated immune response, as T cells can help activate B cells, leading to enhanced antibody production [19].

Moreover, B cells can produce various cytokines that modulate the immune response. For instance, cytokines such as interleukin-10 (IL-10) can have regulatory effects, suppressing excessive inflammation and promoting immune tolerance. This dual functionality allows B cells to not only drive immune responses but also to prevent tissue damage caused by overactive immune reactions [3].

In summary, B cells are integral to immune function through their capacity to produce antibodies, act as antigen-presenting cells, and secrete cytokines that influence both humoral and cellular immune responses. Their multifaceted roles underscore their importance in maintaining immune homeostasis and responding effectively to infections and other immune challenges [1][26][27].

5 Memory B Cells and Immune Memory ​

5.1 Formation and maintenance of memory B cells ​

B cells play a pivotal role in the immune system, primarily through their ability to produce antibodies that recognize, neutralize, and eliminate pathogens. This function is crucial for establishing humoral immunity, which is characterized by the formation and maintenance of memory B cells. The process begins with the activation of naive B cells upon encountering specific antigens, which leads to their differentiation into memory B cells and antibody-secreting plasma cells. During this differentiation, B cells undergo critical molecular events, including immunoglobulin (Ig) class switching and somatic hypermutation, resulting in the generation of high-affinity, antigen-specific antibodies. These processes enable the immune system to respond effectively to subsequent infections by the same pathogen, providing long-lived immunity[8].

Memory B cells are long-lived cells that persist after the initial immune response and are essential for rapid and robust antibody production upon re-exposure to the same antigen. Upon encountering the antigen again, these memory B cells can quickly differentiate into antibody-secreting cells or germinal center B cells, thereby facilitating a more efficient and effective immune response compared to naive B cells[28]. The generation of memory B cells is influenced by various factors, including the cytokine signaling pathways that govern their differentiation and maintenance. For instance, specific cytokines are crucial for promoting memory B cell formation and regulating Ig class switching, which is essential for balancing protective and allergic immune responses[20].

Recent studies have highlighted the significance of memory B cell subsets, which exhibit diverse phenotypic and functional characteristics. These subsets contribute to the adaptability of the immune memory response, allowing for effective responses against different pathogens and variants[29]. Additionally, the environment in which memory B cells develop, particularly the inflammatory context, can shape their functional properties and longevity, impacting their ability to respond to infections[28].

Moreover, the presence of abnormal B cell subsets and functions has been implicated in various diseases, including autoimmunity and allergies. Understanding the molecular mechanisms underlying memory B cell formation and function is critical for developing effective vaccines and therapeutic strategies to enhance immune responses or mitigate immune dysregulation[7].

In summary, B cells are integral to the immune response, with memory B cells serving as a cornerstone of immunological memory. Their ability to rapidly respond to previously encountered antigens, coupled with the regulatory mechanisms that govern their formation and maintenance, underscores their essential role in protecting against infections and maintaining immune homeostasis.

5.2 Role in vaccination and long-term immunity ​

B cells play a pivotal role in the immune response, particularly in the establishment of immunological memory and the effectiveness of vaccinations. Memory B cells are a specialized subset of B cells that are long-lived and generated following an initial exposure to an antigen through infection or vaccination. Upon re-encounter with the same antigen, these cells rapidly differentiate into antibody-secreting plasma cells or germinal center B cells, thus contributing to a swift and robust immune response [28].

The generation of memory B cells is essential for long-term protective immunity. Following vaccination, memory B cells provide a rapid response to subsequent infections by producing high-affinity antibodies. This rapid reactivation and differentiation are crucial for preventing reinfection by pathogens, especially those that may vary over time, such as viruses [30]. Furthermore, the presence of diverse memory B cell populations allows the immune system to adapt to different pathogens and their variants, enhancing the overall efficacy of vaccines [29].

Research has highlighted that the inflammatory environment in which memory B cells develop significantly influences their phenotype and functional capabilities [28]. For instance, during type 1 and type 2 immune responses, different signaling pathways and transcription factors are involved in the development of memory B cells, which can affect their ability to produce antibodies and provide long-term immunity [31].

In the context of vaccination, the effectiveness of a vaccine is closely tied to its ability to induce a strong memory B cell response. Studies have shown that antigen presentation by B cells is critical for the induction of memory T-helper (TH) 1 cell responses, which are necessary for a robust memory response [24]. The durability of this memory is influenced by factors such as the frequency of memory B cells and their longevity, which are essential for maintaining immunological memory over time [32].

Moreover, understanding the heterogeneity of memory B cell populations is vital for improving vaccine efficacy. Different subsets of memory B cells exhibit distinct functional characteristics and responses to antigens, which can be leveraged to enhance the design of vaccines targeting various pathogens [33]. The ongoing research into the cellular and molecular mechanisms governing memory B cell responses is crucial for developing more effective vaccines, particularly against challenging diseases such as malaria and HIV [31].

In summary, B cells, particularly memory B cells, are integral to the immune system's ability to remember and respond to pathogens. Their role in vaccination and the establishment of long-term immunity is underscored by their capacity to rapidly produce antibodies upon re-exposure to antigens, their diverse functional subsets, and the importance of the microenvironment in which they develop. These factors collectively inform vaccine development and the strategies employed to enhance immune memory against infectious diseases.

6 Regulatory B Cells and Immune Regulation ​

6.1 Function and mechanisms of regulatory B cells ​

B cells are pivotal components of the immune system, traditionally recognized for their role in antibody production and T cell activation through antigen presentation. However, recent research has illuminated their crucial regulatory functions, particularly in the context of immune homeostasis and the suppression of inflammatory responses.

Regulatory B cells (Bregs) represent a specialized subset of B cells that exert immunoregulatory effects, primarily through the production of anti-inflammatory cytokines such as interleukin-10 (IL-10), IL-35, and transforming growth factor-beta (TGF-β) [34][35]. These cells play a significant role in modulating immune responses in various conditions, including autoimmune diseases, allergies, infections, and cancer [34].

The mechanisms by which Bregs exert their regulatory functions are diverse. They can suppress the activation and proliferation of effector T cells, thereby reducing the overall inflammatory response [34]. Additionally, Bregs can influence other immune cells, such as dendritic cells and macrophages, through direct cell-cell interactions and the secretion of regulatory cytokines [35][36]. This multifaceted approach enables Bregs to maintain immune tolerance and prevent excessive inflammation, which is critical in autoimmune contexts where the immune system erroneously targets self-antigens [37].

Specific phenotypic markers have been identified that characterize regulatory B cells, such as CD1d(hi)CD5(+) and CD1d(hi)CD21(hi)CD23(+) in murine models [36]. These markers are indicative of their functional capacity to produce IL-10 and modulate immune responses. In humans, similar populations have been identified, including CD19(+)CD24(hi)CD38(hi) B cells, which also exhibit regulatory functions [36].

Bregs can be induced by various stimuli, including microbial products, inflammatory cytokines, and CD40 ligation [34]. This induction process highlights the adaptability of Bregs in responding to environmental cues, allowing them to exert their regulatory effects in a context-dependent manner.

In the context of autoimmune diseases, Bregs are found to be numerically deficient or dysfunctional, which contributes to the pathogenesis of conditions such as systemic lupus erythematosus and rheumatoid arthritis [38]. This underscores the potential therapeutic implications of enhancing Breg function or restoring their numbers as a strategy for treating autoimmune disorders.

Overall, the regulatory functions of B cells, particularly through the actions of regulatory B cells, represent a crucial aspect of immune regulation, providing a balance between effective immune responses and the prevention of autoimmunity and chronic inflammation. Understanding the mechanisms and pathways involved in Breg function may lead to novel therapeutic strategies aimed at modulating immune responses in various disease states.

6.2 Implications in autoimmunity and tolerance ​

B cells play a multifaceted role in immune function, contributing significantly to both the humoral immune response and immune regulation. Traditionally recognized for their ability to produce antibodies, B cells also engage in antigen presentation and cytokine secretion, thereby influencing T cell responses and overall immune homeostasis. Their involvement extends beyond mere antibody production to include critical regulatory functions that are essential for maintaining immune tolerance and preventing autoimmunity.

Regulatory B cells (Bregs) are a specific subset of B cells that have garnered attention for their ability to suppress inflammatory responses and promote tolerance. These cells are characterized by their production of anti-inflammatory cytokines such as IL-10, IL-35, and TGF-β. For instance, IL-10-producing B cells, known as B10 cells, have been extensively studied and are recognized for their role in inhibiting pro-inflammatory responses in various autoimmune conditions, including systemic lupus erythematosus and rheumatoid arthritis [38][39].

Research has shown that regulatory B cells are numerically deficient or functionally impaired in several autoimmune diseases. For example, in systemic lupus erythematosus and anti-neutrophil cytoplasmic antibody-associated vasculitis, the dysfunction of Bregs contributes to exacerbated disease symptoms and loss of immune tolerance [38]. The balance between effector B cells, which promote inflammation, and regulatory B cells is crucial in determining the outcome of immune responses. Dysregulation of this balance can lead to autoimmune pathology, highlighting the importance of Bregs in disease prevention [40].

The mechanisms through which regulatory B cells exert their effects are diverse and include direct suppression of effector T cell responses, modulation of cytokine environments, and interaction with other immune cells. For instance, Bregs can influence T cell activation and differentiation, thereby shaping the overall immune response [41]. Furthermore, recent studies suggest that regulatory B cells can function independently of IL-10, indicating a broader spectrum of regulatory mechanisms that warrant further investigation [42].

In terms of therapeutic implications, targeting B cells in autoimmune diseases has emerged as a promising strategy. Therapies that selectively deplete pathogenic effector B cells while preserving regulatory subsets could restore immune balance and ameliorate disease symptoms. Current clinical research is exploring B cell-targeted biologics, with early results showing potential efficacy in various immune-mediated conditions [38][43].

In conclusion, B cells are integral to immune function, serving as both effector cells that produce antibodies and as regulatory cells that maintain tolerance and prevent autoimmunity. The characterization and understanding of regulatory B cells, particularly their mechanisms of action and therapeutic potential, represent an evolving area of research with significant implications for the treatment of autoimmune diseases.

7 Conclusion ​

This review highlights the multifaceted roles of B cells in immune function, emphasizing their critical contributions to both adaptive immunity and immune regulation. The development and differentiation of B cells, originating from hematopoietic stem cells in the bone marrow, are tightly regulated processes that ensure the generation of a diverse and functional B cell repertoire capable of responding to a wide range of antigens while maintaining self-tolerance. B cells are not only responsible for antibody production but also serve as antigen-presenting cells that facilitate T cell activation, underscoring their importance in orchestrating humoral and cellular immune responses. The generation of memory B cells is crucial for long-term immunity, allowing for rapid and effective responses upon re-exposure to pathogens. Additionally, regulatory B cells play an essential role in modulating immune responses and maintaining tolerance, which is particularly relevant in the context of autoimmune diseases. Future research should focus on elucidating the complex mechanisms underlying B cell functions, exploring the heterogeneity of B cell populations, and investigating their therapeutic potential in various clinical settings, including vaccination strategies and autoimmune disease management.

References ​

  • [1] Pattraporn Satitsuksanoa;Sayuri Iwasaki;Jolien Boersma;Manal Bel Imam;Stephan R Schneider;Iris Chang;Willem van de Veen;Mübeccel Akdis. B cells: The many facets of B cells in allergic diseases.. The Journal of allergy and clinical immunology(IF=11.2). 2023. PMID:37247640. DOI: 10.1016/j.jaci.2023.05.011.
  • [2] Jennifer H Anolik;R John Looney;Frances E Lund;Troy D Randall;Iñaki Sanz. Insights into the heterogeneity of human B cells: diverse functions, roles in autoimmunity, and use as therapeutic targets.. Immunologic research(IF=3.1). 2009. PMID:19350211. DOI: 10.1007/s12026-009-8096-7.
  • [3] Simon Fillatreau. Regulatory functions of B cells and regulatory plasma cells.. Biomedical journal(IF=4.4). 2019. PMID:31627865. DOI: 10.1016/j.bj.2019.05.008.
  • [4] Claudia Mauri;Paul A Blair. Regulatory B cells in autoimmunity: developments and controversies.. Nature reviews. Rheumatology(IF=32.7). 2010. PMID:20856268. DOI: 10.1038/nrrheum.2010.140.
  • [5] Yves Renaudineau;Jacques-Olivier Pers;Boutahar Bendaoud;Christophe Jamin;Pierre Youinou. Dysfunctional B cells in systemic lupus erythematosus.. Autoimmunity reviews(IF=8.3). 2004. PMID:15546800. DOI: 10.1016/j.autrev.2004.07.035.
  • [6] William Hoffman;Fadi G Lakkis;Geetha Chalasani. B Cells, Antibodies, and More.. Clinical journal of the American Society of Nephrology : CJASN(IF=7.1). 2016. PMID:26700440. DOI: 10.2215/CJN.09430915.
  • [7] Yadi Wu;Hanxue Jiang;Yuehong Hu;Haoran Dai;Qihan Zhao;Yang Zheng;Wenbin Liu;Hongliang Rui;Baoli Liu. B cell dysregulation and depletion therapy in primary membranous nephropathy: Prospects and potential challenges.. International immunopharmacology(IF=4.7). 2024. PMID:39098228. DOI: 10.1016/j.intimp.2024.112769.
  • [8] Stuart G Tangye;Joseph Mackie;Karrnan Pathmanandavel;Cindy S Ma. The trajectory of human B-cell function, immune deficiency, and allergy revealed by inborn errors of immunity.. Immunological reviews(IF=8.3). 2024. PMID:37983844. DOI: 10.1111/imr.13288.
  • [9] Joseph J Sabatino;Anne-Katrin Pröbstel;Scott S Zamvil. B cells in autoimmune and neurodegenerative central nervous system diseases.. Nature reviews. Neuroscience(IF=26.7). 2019. PMID:31712781. DOI: 10.1038/s41583-019-0233-2.
  • [10] Manuela Colucci;Julie Oniszczuk;Marina Vivarelli;Vincent Audard. B-Cell Dysregulation in Idiopathic Nephrotic Syndrome: What We Know and What We Need to Discover.. Frontiers in immunology(IF=5.9). 2022. PMID:35140723. DOI: 10.3389/fimmu.2022.823204.
  • [11] Ping Shen;Simon Fillatreau. Suppressive functions of B cells in infectious diseases.. International immunology(IF=3.2). 2015. PMID:26066008. DOI: 10.1093/intimm/dxv037.
  • [12] Sabrina Giampaolo;Gabriela Wójcik;Stefan Klein-Hessling;Edgar Serfling;Amiya K Patra. B cell development is critically dependent on NFATc1 activity.. Cellular & molecular immunology(IF=19.8). 2019. PMID:29907883. DOI: 10.1038/s41423-018-0052-9.
  • [13] S Hokibara;K Agematsu;A Komiyama. B cell development and primary immunodeficiencies with hypogammaglobulinemia.. Archivum immunologiae et therapiae experimentalis(IF=3.9). 2000. PMID:11059643. DOI: .
  • [14] Timothy C Borbet;Marcus J Hines;Sergei B Koralov. MicroRNA regulation of B cell receptor signaling.. Immunological reviews(IF=8.3). 2021. PMID:34523719. DOI: 10.1111/imr.13024.
  • [15] Elisabetta Traggiai;Stefano Volpi;Francesca Schena;Marco Gattorno;Francesca Ferlito;Lorenzo Moretta;Alberto Martini. Bone marrow-derived mesenchymal stem cells induce both polyclonal expansion and differentiation of B cells isolated from healthy donors and systemic lupus erythematosus patients.. Stem cells (Dayton, Ohio)(IF=3.6). 2008. PMID:18024418. DOI: 10.1634/stemcells.2007-0528.
  • [16] Mark C Horowitz;Jackie A Fretz;Joseph A Lorenzo. How B cells influence bone biology in health and disease.. Bone(IF=3.6). 2010. PMID:20601290. DOI: 10.1016/j.bone.2010.06.011.
  • [17] Naomi E Harwood;Facundo D Batista. The cytoskeleton coordinates the early events of B-cell activation.. Cold Spring Harbor perspectives in biology(IF=8.4). 2011. PMID:21047917. DOI: .
  • [18] David J Rawlings;Marc A Schwartz;Shaun W Jackson;Almut Meyer-Bahlburg. Integration of B cell responses through Toll-like receptors and antigen receptors.. Nature reviews. Immunology(IF=60.9). 2012. PMID:22421786. DOI: 10.1038/nri3190.
  • [19] Ichwaku Rastogi;Donghwan Jeon;Jena E Moseman;Anusha Muralidhar;Hemanth K Potluri;Douglas G McNeel. Role of B cells as antigen presenting cells.. Frontiers in immunology(IF=5.9). 2022. PMID:36159874. DOI: 10.3389/fimmu.2022.954936.
  • [20] Stuart G Tangye;Karrnan Pathmanandavel;Cindy S Ma. Cytokine-mediated STAT-dependent pathways underpinning human B-cell differentiation and function.. Current opinion in immunology(IF=5.8). 2023. PMID:36764056. DOI: 10.1016/j.coi.2023.102286.
  • [21] D C Parker. T cell-dependent B cell activation.. Annual review of immunology(IF=33.3). 1993. PMID:8476565. DOI: 10.1146/annurev.iy.11.040193.001555.
  • [22] Theresa Tretter;Ram K C Venigalla;Volker Eckstein;Rainer Saffrich;Serkan Sertel;Anthony D Ho;Hanns-Martin Lorenz. Induction of CD4+ T-cell anergy and apoptosis by activated human B cells.. Blood(IF=23.1). 2008. PMID:18802006. DOI: 10.1182/blood-2008-02-140087.
  • [23] Diana Stoycheva;Hasan Simsek;Willi Weber;Anja E Hauser;Enrico Klotzsch. External cues to drive B cell function towards immunotherapy.. Acta biomaterialia(IF=9.6). 2021. PMID:33636402. DOI: 10.1016/j.actbio.2021.02.026.
  • [24] Natasha Dubois Cauwelaert;Susan L Baldwin;Mark T Orr;Anthony L Desbien;Emily Gage;Kimberly A Hofmeyer;Rhea N Coler. Antigen presentation by B cells guides programing of memory CD4+ T-cell responses to a TLR4-agonist containing vaccine in mice.. European journal of immunology(IF=3.7). 2016. PMID:27701733. DOI: 10.1002/eji.201646399.
  • [25] F Braza;J Chesne;S Castagnet;A Magnan;S Brouard. Regulatory functions of B cells in allergic diseases.. Allergy(IF=12.0). 2014. PMID:25060230. DOI: 10.1111/all.12490.
  • [26] Michael J Townsend;John G Monroe;Andrew C Chan. B-cell targeted therapies in human autoimmune diseases: an updated perspective.. Immunological reviews(IF=8.3). 2010. PMID:20727041. DOI: 10.1111/j.1600-065X.2010.00945.x.
  • [27] Catia Cerqueira;Benoît Manfroi;Simon Fillatreau. IL-10-producing regulatory B cells and plasmocytes: Molecular mechanisms and disease relevance.. Seminars in immunology(IF=7.8). 2019. PMID:31685302. DOI: 10.1016/j.smim.2019.101323.
  • [28] Lizzette Pérez-Pérez;Brian J Laidlaw. Polarization of the memory B-cell response.. Journal of leukocyte biology(IF=3.1). 2025. PMID:39401326. DOI: 10.1093/jleuko/qiae228.
  • [29] Kim L Good-Jacobson. Strength in diversity: Phenotypic, functional, and molecular heterogeneity within the memory B cell repertoire.. Immunological reviews(IF=8.3). 2018. PMID:29944763. DOI: 10.1111/imr.12663.
  • [30] Takeshi Inoue;Tomohiro Kurosaki. Memory B cells.. Nature reviews. Immunology(IF=60.9). 2024. PMID:37400644. DOI: 10.1038/s41577-023-00897-3.
  • [31] Madiha Zahra Syeda;Tu Hong;Chunming Huang;Wenhua Huang;Qingchun Mu. B cell memory: from generation to reactivation: a multipronged defense wall against pathogens.. Cell death discovery(IF=7.0). 2024. PMID:38453885. DOI: 10.1038/s41420-024-01889-5.
  • [32] Ehsan Rezaie;Hekmat Nekoie;Ali Miri;Gholamreza Oulad;Ali Ahmadi;Mojtaba Saadati;Mahmood Bozorgmehr;Marzieh Ebrahimi;Jafar Salimian. Different frequencies of memory B-cells induced by tetanus, botulinum, and heat-labile toxin binding domains.. Microbial pathogenesis(IF=3.5). 2019. PMID:30528250. DOI: 10.1016/j.micpath.2018.12.003.
  • [33] Noel T Pauli;Carole J Henry Dunand;Patrick C Wilson. Exploiting human memory B cell heterogeneity for improved vaccine efficacy.. Frontiers in immunology(IF=5.9). 2011. PMID:22566866. DOI: 10.3389/fimmu.2011.00077.
  • [34] Kirstin Jansen;Lacin Cevhertas;Siyuan Ma;Pattraporn Satitsuksanoa;Mübeccel Akdis;Willem van de Veen. Regulatory B cells, A to Z.. Allergy(IF=12.0). 2021. PMID:33544905. DOI: 10.1111/all.14763.
  • [35] Yoshihiro Baba;Yuichi Saito;Yasuaki Kotetsu. Heterogeneous subsets of B-lineage regulatory cells (Breg cells).. International immunology(IF=3.2). 2020. PMID:31630184. DOI: 10.1093/intimm/dxz068.
  • [36] Manabu Fujimoto. Regulatory B cells in skin and connective tissue diseases.. Journal of dermatological science(IF=4.0). 2010. PMID:20832998. DOI: 10.1016/j.jdermsci.2010.08.010.
  • [37] Xiaoxiao Li;Jonathan Braun;Bo Wei. Regulatory B cells in autoimmune diseases and mucosal immune homeostasis.. Autoimmunity(IF=3.1). 2011. PMID:20701454. DOI: 10.3109/08916931003782189.
  • [38] Kristine Oleinika;Claudia Mauri;Alan D Salama. Effector and regulatory B cells in immune-mediated kidney disease.. Nature reviews. Nephrology(IF=39.8). 2019. PMID:30443016. DOI: 10.1038/s41581-018-0074-7.
  • [39] Geunwoong Noh;Jae Ho Lee. Regulatory B cells and allergic diseases.. Allergy, asthma & immunology research(IF=4.3). 2011. PMID:21738882. DOI: 10.4168/aair.2011.3.3.168.
  • [40] Takashi Matsushita. Regulatory and effector B cells: Friends or foes?. Journal of dermatological science(IF=4.0). 2019. PMID:30514664. DOI: 10.1016/j.jdermsci.2018.11.008.
  • [41] Tomomitsu Miyagaki;Manabu Fujimoto;Shinichi Sato. Regulatory B cells in human inflammatory and autoimmune diseases: from mouse models to clinical research.. International immunology(IF=3.2). 2015. PMID:25957264. DOI: 10.1093/intimm/dxv026.
  • [42] Melisa Gorosito Serrán;Facundo Fiocca Vernengo;Cristian G Beccaria;Eva V Acosta Rodriguez;Carolina L Montes;Adriana Gruppi. The regulatory role of B cells in autoimmunity, infections and cancer: Perspectives beyond IL10 production.. FEBS letters(IF=3.0). 2015. PMID:26424657. DOI: .
  • [43] Wenbo Sun;Can Zhu;Yuxin Li;Xinfeng Wu;Xiaofei Shi;Wanli Liu. B cell activation and autoantibody production in autoimmune diseases.. Best practice & research. Clinical rheumatology(IF=4.8). 2024. PMID:38326197. DOI: 10.1016/j.berh.2024.101936.

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