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Dendritic Cell-Independent B Cell Activation During Acute Virus Infection: A Role for Early CCR7-Driven B-T Helper Cell Collaboration¹

Elke Scandella^2,3,*, Katja Fink^2,, Tobias Junt, Beatrice M. Senn, Evelyn Lattmann^*, Reinhold Förster, Hans Hengartner and Burkhard Ludewig^3,*

^* Research Department, Kantonal Hospital St. Gallen, St. Gallen, Switzerland, Institute of Experimental Immunology, University Hospital Zurich, Zurich, Switzerland, Hannover Medical School, Institute of Immunology, Hannover, Germany

This study provides a detailed spatiotemporal interaction analysis between B cells, Th cells, and dendritic cells (DC) during the generation of protective antiviral B cell immunity. Following vesicular stomatitis virus (VSV) infection, conditional ablation of CD11c-positive DC at the time-point of infection did not impair extrafollicular plasma cell generation and Ig class switching. In contrast, the generation of Th and B cell responses following immunization with recombinant VSV-glycoprotein was DC-dependent. Furthermore, we show that the CCR7-dependent interplay of the three cell-types is crucial for virus-neutralizing B cell responses in the presence of limiting amounts of Ag. An immediate event following VSV infection was the CCR7-mediated interaction of VSV-specific B and Th cells at the T cell-B cell zone border that facilitated plasma cell differentiation and Th cell activation. Taken together, these experiments provide evidence for a direct, CCR7-orchestrated and largely DC-independent mutual activation of Th cells and Ag-specific B cells that is most likely a critical step during early immune responses against cytopathic viruses.

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 received financial support from the Kanton St. Gallen, Switzerland.

² E.S. and K.F. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Elke Scandella, Research Department, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland. E-mail address: elke.scandella{at}kssg.ch or Dr. Burkhard Ludewig, Research Department, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland. E-mail address: burkhard.ludewig{at}kssg.ch

⁴ Abbreviations used in this paper: TI, T cell independent; DC, dendritic cell; DT, diphtheria toxin; DTR, diphtheria toxin receptor transgenic; TD, T cell dependent; MZ, marginal zone; VSV, vesicular stomatitis virus; VSV-G, VSV-glycoprotein; VSV-IND, VSV Indiana.

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