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Science 330 (6007): 1095-1099

Copyright © 2010 by the American Association for the Advancement of Science

Mcl-1 Is Essential for Germinal Center Formation and B Cell Memory

Ingela Vikstrom,1 Sebastian Carotta,1 Katja Lüthje,1 Victor Peperzak,1 Philipp J. Jost,1 Stefan Glaser,1 Meinrad Busslinger,2 Philippe Bouillet,1,3 Andreas Strasser,1,3 Stephen L. Nutt,1,3 David M. Tarlinton1,3,*

Abstract: Lymphocyte survival during immune responses is controlled by the relative expression of pro- and anti-apoptotic molecules, regulating the magnitude, quality, and duration of the response. We investigated the consequences of deleting genes encoding the anti-apoptotic molecules Mcl1 and Bcl2l1 (Bcl-xL) from B cells using an inducible system synchronized with expression of activation-induced cytidine deaminase (Aicda) after immunization. This revealed Mcl1 and not Bcl2l1 to be indispensable for the formation and persistence of germinal centers (GCs). Limiting Mcl1 expression reduced the magnitude of the GC response with an equivalent, but not greater, effect on memory B cell formation and no effect on persistence. Our results identify Mcl1 as the main anti-apoptotic regulator of activated B cell survival and suggest distinct mechanisms controlling survival of GC and memory B cells.

1 Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
2 Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
3 Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.

* To whom correspondence should be addressed. E-mail: tarlinto{at}wehi.edu.au


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