Extensive studies have suggested a central role of B cells in the autoimmune pathogenesis, as loss of B cell tolerance results in increased serum levels of autoantibodies, enhanced effector T cell response and tissue damages. Here, we provide an overview of dysregulated B cell responses in the development of autoimmunity. In addition to their presence in the target organs, autoreactive B cells can promote the formation of ectopic lymphoid structures and differentiate into plasma cells that produce large amounts of autoantibodies and cytokines. In animal models that recapitulate the key features of human autoimmune disease, mechanistic studies have indicated two categories of autoantibodies (1) serological markers for disease diagnosis and prognosis; (2) effector molecules that induce organ hypofunction or damage directly in an epitope-specific manner, or indirectly by activating other immune cell subsets. Moreover, B cell-derived cytokines usually promote the autoreactive T cell response during autoimmune development, but there is compelling evidence that a subpopulation of B cells negatively regulates immune responses, also known as regulatory B cells via secreting anti-inflammatory cytokines (IL-10, IL-35, etc.) or a contact-dependent fashion. Although B cell depletion could eliminate most circulating B cells in the periphery, the clinical outcomes of B cell depletion therapy for autoimmune diseases vary among individuals due to differential activation or survival signals for B cells provided by tissue microenvironment. Thus, therapeutic combinations that target immune checkpoints and B cell activation may represent a promising strategy for the effective treatment of human autoimmune diseases.Primary antibody deficiencies (PADs) are the most common types of inherited primary immunodeficiency diseases (PIDs) presenting at any age, with a broad spectrum of clinical manifestations including susceptibility to infections, autoimmunity and cancer. Antibodies are produced by B cells, and consequently, genetic defects affecting B cell development, activation, differentiation or antibody secretion can all lead to PADs. Whole exome and whole genome sequencing approaches have helped identify genetic defects that are involved in the pathogenesis of PADs. Here, we summarize the clinical manifestations, causal genes, disease mechanisms and clinical treatments of different types of PADs.Immunoglobulin A (IgA) is the major immunoglobulin isotype produced by the gut immune system, and many studies revealed key roles of IgA in establishing host-bacteria mutualism. This chapter will review current understandings for the function of gut IgA in regulating commensal microbiota. IgA specifically recognizes bacterial species that strongly stimulate host's immune responses, and suppresses their overgrowth or reduces the expressions of bacterial pro-inflammatory genes. On the other hand, IgA coatings on symbiotic bacteria enhance bacteria-mucus and bacteria-bacteria interactions, which induce production of metabolites enforcing mucosal barrier functions. Such diversified effects suggest that multiple factors may be involved in the mechanisms of IgA-bacteria interactions, including IgA specificity to microbial epitopes, mode of cellular responses of IgA synthesis (T-dependent and T-independent) and post-translational modifications of IgA proteins, such as glycosylation.B cells are typically characterized by their ability to produce antibodies, function as secondary antigen-present cells, and produce various immunoregulatory cytokines. The regulatory B (Breg)-cell population is now widely accepted as an important modulatory component of the immune system that suppresses inflammation. Recent studies indicate that Breg-cell populations are small under physiological conditions but expand substantially in both human patients and murine models of chronic inflammatory diseases, autoimmune diseases, infection, transplantation, and cancer. Almost all B-cell subsets can be induced to form Breg cells. In addition, there are unique Breg-cell subsets such as B10 and Tim-1+ B cells. Immunoregulatory function may be mediated by production of cytokines such as IL-10 and TGF-β and ensuing suppression of T cells, by direct cell-cell interactions, and (or) by altering the immune microenvironment. In this chapter, we describe in detail the discovery of Breg cells, their phenotypes, differentiation, function, contributions to disease, and therapeutic potential.Immunoglobulin (Ig) M is the first antibody isotype produced during an immune response and is critical for host defense against infections. Recent studies have revealed that IgM also plays an important role in immune regulation and immunological tolerance. Mice lacking secretory IgM not only exhibit impaired production of antigen-specific IgG and are more susceptible to bacterial and viral infections, but also produce autoantibodies and are prone to develop autoimmune diseases. For many years, IgM has been thought to function predominantly by binding to antigen and activating complement (C') system. It is now clear that IgM can also elicit its function through the IgM Fc receptor (FcμR). In this chapter, we will review the role of FcμR in B cell development, maturation, survival and activation, antibody production, host defense against bacterial and viral infections, and B cell tolerance. We will also discuss the relative contribution of IgM-C' and IgM-FcμR pathways in humoral immune responses. Finally, we will discuss the possible involvement of FcμR in human chronic lymphocytic leukemia.Humoral immunity provides protection from pathogen infection, and this is mediated by antibodies that are produced by plasma cells. Plasma cells are terminally differentiated from activated B cells and are specialized for secreting antibodies. Plasma cells are generated during extrafollicular or germinal center (GC) responses, but GC-derived plasma cells are thought to be the major precursors of long-lived plasma cells, which confer long-term protection.  https://www.selleckchem.com/products/zanubrutini-bgb-3111.html  Here, we review recent progress in our understanding of the cellular and molecular basis for plasma cell differentiation from GC B cells.