Identification of Anergic B Cells within a Wild-Type Repertoire
2006; Cell Press; Volume: 25; Issue: 6 Linguagem: Inglês
10.1016/j.immuni.2006.10.017
ISSN1097-4180
AutoresKevin T. Merrell, Robert J. Benschop, Stephen B. Gauld, Katja Aviszus, Débora Decoté‐Ricardo, Lawrence J. Wysocki, John C. Cambier,
Tópico(s)Immunotherapy and Immune Responses
ResumoSummary The contribution of anergy to silencing of autoreactive B cells in physiologic settings is unknown. By comparing anergic and nonanergic immunoglobulin-transgenic mouse strains, we defined a set of surface markers that were used for presumptive identification of an anergic B cell cohort within a normal repertoire. Like anergic transgenic B cells, these physiologic anergic cells exhibited high basal intracellular free calcium and did not mobilize calcium, initiate tyrosine phosphorylation, proliferate, upregulate activation markers, or mount an immune response upon antigen-receptor stimulation. Autoreactive B cells were overrepresented in this cohort. On the basis of the frequency and lifespan of these cells, it appears that as many as 50% of newly produced B cells are destined to become anergic. In conclusion, our findings indicate that anergy is probably the primary mechanism by which autoreactive B cells are silenced. Thus maintenance of the unresponsiveness of anergic cells is critical for prevention of autoimmunity.
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