Journal article
Mcl-1 is essential for germinal center formation and B cell memory
I Vikstrom, S Carotta, K Lüthje, V Peperzak, PJ Jost, S Glaser, M Busslinger, P Bouillet, A Strasser, SL Nutt, DM Tarlinton
Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2010
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-x L) 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 e..
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Awarded by National Cancer Institute
Funding Acknowledgements
This work was supported in part by grants from the National Health and Medical Research Council (NHMRC) Australia (356202 to D. M. T. and S.L.N. and 461221 to P. B. and A. S.), the Leukemia and Lymphoma Society (SCOR grant 7413), and the NIH (CA43540 and CA80188). D. M. T. and A. S. are supported by fellowships from the NHMRC; S.L.N. by a Pfizer Australia Research Fellowship; I. V. by the Olle Engkvist Byggmastare and Wenner-Gren Foundations; K. L. by a fellowship from the German Academic Exchange Service; P. B. by the Charles and Sylvia Viertel Charitable Foundation; and M. B. by Boehringer Ingelheim. DNA sequence data are available in GenBank (accession number HM804028-HM804084). We are indebted to the facilities of our respective institutes, particularly those responsible for animal husbandry and flow cytometry. We also acknowledge the assistance of L. O'Reilly for Western blot antibodies and the many helpful discussions with members of the Walter and Eliza Hall Institute B Cell Program. Author contributions are as follows: I. V. and D. M. T. designed the research; I. V., K. L., S. G., V. P., S. C., and P.J. performed experiments and contributed to interpretation and discussion; M. B., P. B., A. S., and S.L.N. contributed to the design of experiments, interpretation of results, and drafting the manuscript; I. V., K. L., and V. P. analyzed data and prepared figures; and I. V. and D. M. T. wrote the manuscript.