T cell-independent rescue of B lymphocytes from peripheral immune tolerance.
Autoimmunity arises when immune tolerance to specific self-antigens is broken. The mechanisms leading to such a failure remain poorly understood. One hypothesis proposes that infectious agents or antigens can break B or T lymphocyte self-tolerance by expressing epitopes that mimic self. Using a transgenic immunoglobulin model, we show that challenge with self-mimicking foreign antigen rescues B cells from peripheral tolerance independent of T cell help, resulting in the accumulation of self-reactive cells in the lymph nodes and secretion of immunoglobulins that bind to a liver-expressed self-antigen. Therefore, our studies reveal a potentially important mechanism by which B lymphocytes can escape self-tolerance.
Kouskoff
V
V
Department of Pediatrics, Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
Lacaud
G
G
Nemazee
D
D
D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D017637:Clonal Deletion; D003429:Cross Reactions; D006183:H-2 Antigens / Q000276:immunology; D007114:Immunization; D007075:Immunoglobulin M / Q000032:analysis; D008099:Liver / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D018716:Molecular Mimicry; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology
D000955:Antigens, T-Independent; D001323:Autoantibodies; D001324:Autoantigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell