B cell diversity and longevity in systemic autoimmunity.
Despite much investigation, the nature of the primary disturbances that culminate in the production of pathogenic autoantibodies remains imprecise. However, major advances in the understanding of the genetics, the cellular and the molecular basis of pathogenic autoreactivity have been achieved in recent years. Not only B cells play a paramount role in systemic autoimmunity, but their role is not limited to secretion of autoantibodies. Under certain experimental conditions, B cells can activate memory T cells, and can process and present self-antigens to naive T cells, implying the existence of an antibody-independent mechanism for tissue injury in systemic autoimmune diseases, such as lupus. In both the mouse and the human disease, B cells secreting autoantibodies exhibit features which suggest that they are selected by specific autoantigens. Factors, such as BAFF, that support differentiation of selected B cells into mature long-lived B cells may be critical in generating deleterious autoimmune responses, at least in experimental animals. During these selection processes, the amount of signals received by the B cells are fine-tuned for optimal transmission, and kinases and phosphatases control most activities. Since a tight regulation of signaling pathways is required to prevent overt autoimmunity, faulty cell signaling may cause or exacerbate disorders of the immune system. Several observations showing altered expression of signaling molecules in T and B lymphocytes from patients with human lupus suggest that the subversion of immune receptor signaling could account for the hyperproduction of autoantibodies.
Zouali
Moncef
M
Unité d'Immunopathologie Humaine, Institut National de la Santé et de la Recherche Médicale (INSERM), U 430, 96 rue Didot, Hôpital Broussais, 75674 Paris Cedex 14, France. moncef.zouali@wanadoo.fr
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D015398:Signal Transduction
D001323:Autoantibodies; D007075:Immunoglobulin M