Role of B cell antigen receptor in regulation of V(D)J recombination and cell survival.

B lymphocytes learn through the interaction of the B cell receptor with antigens in the context of B cell developmental stage and environmental cues. B cells can respond by proliferation and antibody secretion, programmed cell death, or modification of the antibody genes themselves through secondary immunoglobulin gene rearrangements or somatic point mutation. A critical learning process is that of self/nonself-discrimination. We have shown that one potent mechanism for immune self-tolerance in B cells is ongoing antibody light chain gene rearrangements, which can result in "receptor editing" that changes antigen receptor specificity. This process appears to be developmentally regulated, because it is confined to cells at an immature stage of development. Cells at later stages of development can be tolerized by apoptosis, but probably not by receptor editing.