B Cell Differentiation: Development of Antibody Repertoires

Abstract

In mammals, primary B cell differentiation occurs as an antigen-independent process in the liver of the fetus and in the bone marrow of the adult. During these stages, stem cells give rise to precursor B lymphocytes — the cells in which antibody variable region genes are assembled from component germline gene segments (reviewed by Alt et al., 1987). The genes that encode Ig heavy and light chain variable regions are assembled at distinct stages of pre-B cell differentiation. First, heavy chain variable region gene is assembled from component V_H, D and J_H segments and subsequently light chain variable region genes are assembled. Functional heavy and light chains associate to form a complete Ig molecule; the expression of this molecule on the cell surface defines the next major stage of B cell differentiation, the B lymphocyte. Only a single heavy chain and a single light chain are expressed on the surface of any particular clonal population of B cells; this ensures B lymphocyte clones will express a single species of Ig with a unique set of binding specificities. Following generation in primary differentiation organs, B cells migrate to peripheral lymphoid organs such as the spleen. Upon appropriate interaction with a cognate antigen, peripheral B lymphocytes are stimulated to further mature into antibody-secreting cells. During this antigen-driven clonal selection process, additional types of B lineage cells may be generated including cells that have undergone heavy chain class-switching or somatic mutational events.