The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online September 22, 2008
doi:10.1084/jem.20070731
The Journal of Experimental Medicine, Vol. 205, No. 10, 2437-2448
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Kim et al.
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ARTICLE

 Increased IL-12 inhibits B cells' differentiation to germinal center cells and promotes differentiation to short-lived plasmablasts

Sun Jung Kim1, Michele Caton2, Chuansheng Wang1, Magi Khalil1, Zhi-Jie Zhou1, John Hardin1, and Betty Diamond1,2

1 Autoimmune Disease Laboratory, Feinstein Institute for Medical Research, Manhasset, NY 11030
2 Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461

CORRESPONDENCE Betty Diamond: bdiamond{at}nshs.edu

B cells activated by antigen in T cell–dependent immune responses can become short-lived plasma cells, which remain in the spleen, or germinal center–derived memory or plasma cells, which show evidence of affinity maturation and, in the case of plasma cells, migrate to the bone marrow. We show that this cell fate decision can be governed by the cytokine environment engendered by activated dendritic cells (DCs). DCs from mice lacking the Fc receptor {gamma} chain exhibited an activated phenotype in vitro. They secreted more of the proinflammatory cytokine IL-12, which led to the preferential generation of short-lived splenic plasma cells, with ensuing low affinity antibodies and a diminished recall response. Understanding the factors that regulate antigen-activated B cell differentiation and memory cell formation has implications for both antibody-mediated autoimmune disease and protective antibody responses.

Abbreviations used: AID, activation-induced cytidine deaminase; BMDC, BM-derived DC; dsDNA, double-stranded DNA; MAP, multiple antigenic peptide.

S.J. Kim and M. Caton contributed equally to this paper.

© 2008 Kim et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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