B Cell Development, Activation and Immunoglobulin Structure

Abstract

Antibody production is the hallmark of humoral immunity in the adaptive immune responses. B lymphocytes produce antibodies (immunoglobulins) specific to antigens. B cell development occurs in the bone marrow. Unlike T cells which develop and mature mostly in the thymus, B cells begin development in the bone marrow and begin expression of immunoglobulin (Ig) and expression of B cell surface markers in the bone marrow. In this chapter, we will highlight the features that distinguish B cells from T cells and discuss the markers that define developmental stages of B lymphocytes and allow for the cells to be isolated and studied. A major event that occurs during B cell development is the generation of the variable region of the antibody molecule in the genes that encode the heavy and light chain polypeptides. The antigen binding regions of the antibody molecule are found in the variable regions in the heavy and light chains. Three germ-line genes recombine and rearrange to form the variable region. The heavy (H) chain gene is composed of V (variable), D (diversity) and J (joining) genes. The light (L) chain gene is composed of V and J genes. B lymphocytes differentiate from the common lymphoid progenitor (CLP), with the transcription factors Ikaros, purine box factor 1 (PU.1), early B cell factor-1 (EBF-1) and E2A driving B cell commitment into the B cell lineage. Maturation of the B cell continues following migration and homing of the B cells into secondary lymphoid organs. B cells exhibiting autoreactivity are deleted and negatively selected like the T cells in the thymic medulla, resulting in central tolerance within the bone marrow. Following rearrangement of Ig, autoreactivity is further prevented by receptor-editing of Ig and B cell anergy. B lymphocytes transition through pre-pro, pro and pre B cell stages. Each stage is marked by expression of specific molecules that define the developmental stage.