Regulation of B cell self-tolerance by BAFF.
To avoid the generation of pathogenic autoantibodies, self-reactive lymphocytes are deleted at several distinct checkpoints during B cell maturation. BAFF is required for mature B cell development and survival but causes B cell hyperplasia and autoimmunity when it is overexpressed. Self-reactive B cells have reduced responsiveness to BAFF and therefore die due to the limiting levels of BAFF available in vivo. Elevated BAFF expression subverts B cell self-tolerance by rescuing self-reactive B cells normally deleted relatively late during maturation. Strongly self-reactive B cells are deleted prior to expression of BAFF-R and are therefore resistant to rescue by BAFF.
Brink
Robert
R
Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW, Australia. r.brink@garvan.org.au
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D006965:Hyperplasia; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D016328:NF-kappa B / Q000378:metabolism; D009928:Organ Specificity; D011993:Recombinant Fusion Proteins / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology*; D015398:Signal Transduction
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse