Elimination of germinal-center-derived self-reactive B cells is governed by the location and concentration of self-antigen.

Tyani D Chan, Katherine Wood, Jana R Hermes, Danyal Butt, Christopher J Jolly, Antony Basten, Robert Brink

Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.

Immunity 2012 Nov 16

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Secondary diversification of the B cell repertoire by immunoglobulin gene somatic hypermutation in the germinal center (GC) is essential for providing the high-affinity antibody specificities required for long-term humoral immunity. While the risk to self-tolerance posed by inadvertent generation of self-reactive GC B cells has long been recognized, it has not previously been possible to identify such cells and study their fate. In the current study, self-reactive B cells generated de novo in the GC failed to survive when their target self-antigen was either expressed ubiquitously or specifically in cells proximal to the GC microenvironment. By contrast, GC B cells that recognized rare or tissue-specific self-antigens were not eliminated, and could instead undergo positive selection by cross-reactive foreign antigen and produce plasma cells secreting high-affinity autoantibodies. These findings demonstrate the incomplete nature of GC self-tolerance and may explain the frequent association of cross-reactive, organ-specific autoantibodies with postinfectious autoimmune disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

Tyani D Chan, Katherine Wood, Jana R Hermes, Danyal Butt, Christopher J Jolly, Antony Basten, Robert Brink. Elimination of germinal-center-derived self-reactive B cells is governed by the location and concentration of self-antigen. Immunity. 2012 Nov 16;37(5):893-904