From apoptosis to autoimmunity: Insights from the signaling pathways leading to proliferation or to programmed cell death

B-lymphocyte differentiation proceeds through multiple steps from committed precursor cells into antibody-secreting plasma cells and is defined by changes in the expression pattern of lineage-specific genes. Antigen-independent stages of B-cell maturation take place in the bone marrow, where lymphoid precursors commit to the B lineage and subsequently differentiate into surface IgM super(+) B cells. This differentiation includes the transition from pro-B cells (stage at which the Ig genes are in germline configuration) towards pre-B cells (where VDJ recombination of the Ig variable region in the heavy chain locus generates mu chains that are expressed on the cell surface in association with the surrogate light chains, VpreB and lambda 5). Finally, rearrangements of the Kappa or lambda chains take place and the IgM receptor is displayed on the surface of immature B cells. The transition from immature to mature B cells is accompanied by Ig heavy chain class switching. Later, mature B cells migrate out from bone marrow into the periphery (spleen and lymphnodes), where an antigen-dependent phase of B-cell development takes place.