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Mayer, C.T., Nieke, J.P., Gazumyan, A., Cipolla, M., Wang, Q., Oliveira, Y.T., Ramos, V., Monette, S., Li, Q.Z., Gershwin, M.E., Kashkar, H., Nussenzweig, M.C.

An apoptosis-dependent checkpoint for autoimmunity in memory B and plasma cells


B lymphocytes acquire self-reactivity as an unavoidable byproduct of antibody gene diversification in the bone marrow and in germinal centers (GCs). Autoreactive B cells emerging from the bone marrow are silenced in a series of well-defined checkpoints, but less is known about how self-reactivity that develops by somatic mutation in GCs is controlled. Here, we report the existence of an apoptosis-dependent tolerance checkpoint in post-GC B cells. Whereas defective GC B cell apoptosis has no measurable effect on autoantibody development, disruption of post-GC apoptosis results in accumulation of autoreactive memory B cells and plasma cells, antinuclear antibody production, and autoimmunity. The data presented shed light on mechanisms that regulate immune tolerance and the development of autoantibodies.

Read more at: PNAS