Immunobiology of the immature B cell: plasticity in the B-cell antigen receptor-induced response fine tunes negative selection

The immature and transitional immature B-cell stages define an important wi ndow in B-fell development. as it is at this point that cells committed to the B-cell lineage first express the clonotypic B-cell antigen receptor (BC R) and cells expressing self-reactive specificities may be identified and e liminated. The intrinsic susceptibility of the immature B cell to negative selection following BCR engagement distinguishes these cells functionally f rom mature-stage B cells in which BCR cross-linking leads to activation. Ou r laboratory has been interested in determining the molecular events respon sible for the distinct and disparate responses of immature and mature B cel ls to antigen receptor signaling in order to understand the molecular basis of negative selection of developing B cells. These studies have indicated that developmentally regulated mechanisms, intrinsic to the B cell, regulat e the differential responsiveness of the immature and mature stage B cell t o antigen. Hoc-ever, the "hard-wired" BCR-induced apoptotic response of the immature B cell can be modified by the microenvironmental context in which the antigen is encountered. This plasticity fine tunes the BCR-induced res ponse of the immature B cell by regulating the mechanism of negative select ion and, under defined circumstances, allowing for recruitment into an immu ne response.