Elimination of Germinal Center-Derived Self-Reactive B Cells Is Governed by the Location and Concentration of Self-Antigen
Immunity, 08 November 2012
10.1016/j.immuni.2012.07.017
Authors
Tyani D. Chan, Katherine Wood, Jana R. Hermes, Danyal Butt, Christopher J. Jolly, Antony Basten, Robert Brink
Summary
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.
A summary in Garvan Institute:
http://www.garvan.org.au/news-events/news/how-infection-can-trigger-autoimmune-disease.html
A previous publication of this theory:
Mechanisms for the induction of autoimmunity by infectious agents
Kai W. Wucherpfennig
Published in Volume 108, Issue 8 (October 15, 2001)
J Clin Invest. 2001;108(8):1097–1104. doi:10.1172/JCI14235.
http://www.jci.org/articles/view/14235
La noticia en ABC salud: http://www.abc.es/salud/noticias/20140227/abci-psoriasis-cnio-201402261329.html
En uno de los trabajos, publicado en «Immunity», se demuestra que los síntomas de la enfermedad desaparecen cuando se bloquea una proteína llamada S100A9. En el otro artículo, que aparece en «Science Translational Medicine», se demuestra que esto también sucede si se actúa sobre un ARN no codificante, el micro ARN miR-21.