Approximately 85% of all non-Hodgkin's lymphomas arise from cells of the B lineage. Sequential stages of B-cell development have been defined by molecular markers, and these markers can be used to reclassify lymphoid malignancies as representing maturational arrest and immortalization at specific points in B-cell ontogeny. Several of the factors controlling the ordered rearrangement and expression of the immunoglobulin (Ig) genes have been identified. Signals generated by intermediates in Ig gene rearrangement, as well as by the complete Ig molecule, have been found to be critical in guiding early B-cell development. The processes of peripheral B-cell activation, antigenic affinity maturation, and terminal B-cell differentiation are also highly regulated. The molecular mechanisms responsible for both promoting and attenuating B-cell (humoral) immune responses have been increasingly well defined. This review summarizes some aspects of the current understanding of normal B-cell development, maturation, activation, and death, focusing on the factors implicated in regulating progression through these stages.
