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 window in B-cell development, as it is at this point that cells committed to the B-cell lineage first express the clonotypic B-cell antigen receptor (BCR) and cells expressing self-reactive specificities may be identified and eliminated. The intrinsic susceptibility of the immature B cell to negative selection following BCR engagement distinguishes these cells functionally from mature-stage B cells in which BCR cross-linking leads to activation. Our laboratory has been interested in determining the molecular events responsible for the distinct and disparate responses of immature and mature B cells 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, regulate the differential responsiveness of the immature and mature stage B cell to antigen. However, 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 response of the immature B cell by regulating the mechanism of negative selection and, under defined circumstances, allowing for recruitment into an immune response.
King
L B
LB
University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Monroe
J G
JG
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020013:Calcium Signaling; D002454:Cell Differentiation; D017637:Clonal Deletion; D053222:Fas Ligand Protein; D006801:Humans; D007072:Immunoglobulin D / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D019014:fas Receptor; D011493:Protein Kinase C