B Cells

B cells play a central role in the adaptive immune response as they not only produce antibodies and generate immunological memory, but they also function as antigen-presenting cells, and secrete regulatory cytokines. During embryonic development, B cells originate from hematopoietic stem cells (HSCs) in the fetal liver, and then from HSCs in bone marrow throughout adult life. The initial stages of B cell development occur in the bone marrow and are antigen-independent. These stages are characterized by an ordered sequence of random immunoglobulin gene rearrangements that result in the production of antigenically committed B cells, with each cell expressing a mature B cell receptor with single antigen specificity. This is followed by a negative selection process that is designed to eliminate any self-reactive immature B cells. Most immature B cells then leave the bone marrow and migrate to the spleen where they differentiate into transitional immature B cells that then develop into marginal zone or follicular B cells. Upon antigen exposure, marginal zone B cells are preferentially activated in a T cell-independent manner, while follicular B cells are preferentially activated in a T cell-dependent manner. Marginal zone B cells typically differentiate into short-lived plasmablasts that rapidly produce low affinity antibodies following activation, while follicular B cells differentiate into either short-lived plasmablasts or memory B cells outside of the lymphoid follicles or enter a lymphoid follicle and form a germinal center. In the germinal center, follicular B cells proliferate, undergo immunoglobulin class switch recombination, and interact with follicular helper T (Tfh) cells, which help direct affinity maturation and the differentiation of follicular B cells into either long-lived plasma cells or memory B cells. Long-lived plasma cells produce large amounts of high affinity antibodies and can remain either in the secondary lymphoid organs or return to the bone marrow, while memory B cells typically remain in the secondary lymphoid organs or enter the circulation. The number of memory B cells rapidly declines following the primary B cell response, but low numbers of these cells persist for long periods of time. Upon re-exposure to the initial antigen, memory B cells proliferate, differentiate into plasmablasts or plasma cells, and provide a more rapid antibody response compared to naïve B cells. Defects in B cell development, selection, and functions have been found to be associated with chronic inflammation and autoimmune diseases, immunodeficiencies, and specific types of cancer.