Introduction to B-2 Cells
Based on their different origins and functions, B cells can be divided into two types: B-1 cells and B-2 cells. B-2 cells are classical B lymphocytes that mainly exist in peripheral blood and lymphoid organs, accounting for approximately 45% of peripheral blood B lymphocytes. After first encountering an antigen, B-2 cells undergo clonal expansion and, with the help of T cells, produce high-affinity IgM antibodies. These B-2 cells undergo affinity maturation in the germinal center and, through gene rearrangement and high-frequency mutation, generate memory B cells and long-lived plasma cells that continuously produce high-affinity IgM antibodies. In the germinal center, B-2 cells acquire highly diverse antigen specificity through gene rearrangement and high-frequency mutation. T cells release cytokines such as IL-21, supporting the growth, differentiation, and class switching of B-2 cells. The binding of CD40 and CD40 ligand can also promote B-2 cell immune responses. Finally, the germinal center reaction gives rise to affinity-matured IgM memory B cells and plasma cells. The high-affinity IgM antibodies produced by B-2 cells can effectively eliminate pathogens. After surviving, IgM memory B cells can quickly initiate IgM and IgG antibody responses upon re-infection with the same pathogen. Therefore, the presence of IgM+ memory B cells marks the activation of humoral immune response.
Fig.1 Mechanisms of differentiation of B-2 cells.1
IgM Antibodies Produced by B-2 Cells
IgM antibodies derived from B-2 cells have been used in research to assess the pathologic evaluation of antibody-mediated rejection (AMR) in transplantation. However, generating monoclonal IgM antibodies from B-2 cells can present certain challenges. Most IgM antibodies in serum are natural antibodies produced by B-1 cells, so it is necessary to selectively detect monoclonal IgM antibodies derived from B-2 cells. One approach is to use an analysis system of peripheral blood mononuclear cells (PBMCs) to analyze the antigen specificity of circulating IgM+ memory B cells (mBCs), in order to avoid interference from natural antibodies. Another approach involves treating cells with fluorescent beads that bind to antigens to detect B cells expressing monoclonal antibodies (mAbs) at a single-cell level. However, further research is required to understand the conditions that induce differentiation of IgM+ B-2 cells into antibody-producing cells, particularly in vivo, as the presence of helper cells may inhibit the differentiation process. Before widespread application of IgM antibodies in clinical settings, such as standard care or diagnostic procedures, several issues need to be addressed, including clarifying the conditions that induce differentiation of IgM+ B-2 cells into antibody-producing cells, understanding the mechanisms by which IgM antibodies contribute to graft survival, and evaluating the clinical significance of IgM antibodies in the context of AMR.
The pentameric structure of IgM antibodies gives them high affinity and potent complement activation. The role of IgM antibodies in transplant rejection is complex, and further studies are needed to determine whether it has protective or deleterious effects. Detection of IgM memory B cells and donor-specific IgM antibodies can help assess the risk of rejection. IgM immunoglobulin therapy may modulate autoimmunity and inflammation, but production of antigen-specific IgM antibodies for therapeutic use remains challenging. In conclusion, IgM is an important innate and acquired immune antibody produced by B-1 and B-2 cells. An in-depth study of the role of different sources of IgM antibodies will help to understand immune mechanisms and diseases such as transplant rejection.
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Reference
- Matsuda, Yoshiko, et al. “Characteristics of immunoglobulin M type antibodies of different origins from the immunologic and clinical viewpoints and their application in controlling antibody-mediated allograft rejection.” Pathogens 10.1 (2020): 4.
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