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The Journal of Immunology, 2007, 179: 5877-5885.
Copyright © 2007 by The American Association of Immunologists, Inc.

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B Cell Activation State-Governed Formation of Germinal Centers following Viral Infection1

Katja Fink2,3,4,*, Nataly Manjarrez-Orduño3,5,*, Anita Schildknecht*, Jacqueline Weber*, Beatrice M. Senn{dagger}, Rolf M. Zinkernagel* and Hans Hengartner*

* Institute of Experimental Immunology, University Hospital, Zurich, Switzerland; and {dagger} Intercell AG, Vienna, Austria

Germinal centers are structures that promote humoral memory cell formation and affinity maturation, but the triggers for their development are not entirely clear. Activated extrafollicular B cells can form IgM-producing plasmablasts or enter a germinal center reaction and differentiate into memory or plasma cells, mostly of the IgG isotype. Vesicular stomatitis virus (VSV) induces both types of response, allowing events that promote each of these pathways to be studied. In this work, extrafollicular vs germinal center responses were examined at a cellular level, analyzing VSV-specific B cells in infected mice. We show that VSV-specific germinal centers are transiently formed when insufficient proportions of specific T cell help is available and that strong B cell activation in cells expressing high levels of the VSV-specific BCR promoted their differentiation into early blasts, whereas moderate stimulation of B cells or interaction with Th cells restricted extrafollicular responses and promoted germinal center formation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by Swiss National Foundation Grants 3100AO-100068/1 and 3100AO-100779/1.

2 Current address: Novartis Institute for Tropical Diseases, 10 Biopolis Road, 138670 Singapore.

3 K.F. and N.M.-O. contributed equally to this study.

4 Address correspondence and reprint requests to Dr. Katja Fink, Novartis Institute for Tropical Diseases, 10 Biopolis Road, 05-01 Chromos, 138670 Singapore. E-mail address: katja.fink{at}novartis.com

5 Current address: Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642.

6 Abbreviations used in this paper: GC, germinal center; ASC, Ab-secreting cell; VSV, vesicular stomatitis virus; VSV-IND, VSV, Indiana; LCMV, lymphocytic choriomeningitis virus; NP, (4-hydroxy-3-nitrophenyl)acetyl; tg, transgenic.







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