B cell receptor revision diminishes the autoreactive B cell response after antigen activation in mice.
Autoreactive B cells are regulated in the BM during development through mechanisms, including editing of the B cell receptor (BCR), clonal deletion, and anergy. Peripheral B cell tolerance is also important for protection from autoimmune damage, although the mechanisms are less well defined. Here we demonstrated, using a mouse model of SLE-like serology, that during an autoimmune response, RAG was reinduced in antigen-activated early memory or preplasma B cells. Expression of RAG was specific to antigen-reactive B cells, required the function of the IL-7 receptor (IL-7R), and contributed to maintenance of humoral tolerance. We also showed that soluble antigen could diminish a non-autoreactive antibody response through induction of BCR revision. These data suggest that tolerance induction operates in B cells at a postactivation checkpoint and that BCR revision helps regulate autoreactivity generated during an ongoing immune response.
Wang
Ying-Hua
YH
Department of Microbiology, Columbia University Medical Center, New York, New York, USA.
Diamond
Betty
B
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D020395:Receptors, Interleukin-7 / Q000276:immunology / Q000378:metabolism; D012995:Solubility
D000941:Antigens; D001324:Autoantigens; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; D020395:Receptors, Interleukin-7; C064658:RAG-1 protein