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The Journal of Immunology, 2007, 179: 7316-7324.
Copyright © 2007 by The American Association of Immunologists, Inc.

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A New Role of CTLA-4 on B Cells in Thymus-Dependent Immune Responses In Vivo1

Dagmar Quandt*,{dagger}, Holger Hoff*,{dagger},{ddagger}, Marion Rudolph*,{dagger},{ddagger}, Simon Fillatreau* and Monika C. Brunner-Weinzierl2,*,{dagger},{ddagger}

* Deutsches Rheuma-Forschungszentrum, Berlin; {dagger} Klinik für Innere Medizin mit Schwerpunkt Rheumatologie und Klinischer Immunologie, Charité-Universitätsmedizin, Berlin, Germany; and {ddagger} Klinik für Pädiatrie, Otto von Guericke Universität Magdeburg, Magdeburg, Germany

The expression of CTLA-4 (CD152) on the cell surface of B cells and its consequences for the humoral immune response in vivo are unknown. We investigated the expression of CTLA-4 mRNA and protein in B cells in T cell-independent or -dependent ways. B cells in the presence of Ag-stimulated Th2 cells expressed mRNA of CTLA-4 and up-regulated intracellular CTLA-4 protein. Using a liposome-enhanced staining technique, we show for the first time, that surface CTLA-4 protein is expressed by 11–15% of B cells in a T cell-dependent culture system. To dissect the role of CTLA-4 on B cells in vivo, we used bone marrow chimeric mice in which only B cells were CTLA-4 deficient. These mice showed that early B cell development and homeostasis is not influenced by CTLA-4 deficiency of B cells. Ag-specific responses after immunization of the chimeric mice revealed elevated levels of IgM Abs in mice deficient for B cell CTLA-4. We propose that CTLA-4 signals on B cells determine the early fate of B cells in thymus-dependent immune responses.

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 the Deutsche Forschungsgemeinschaft Br1860, Deutscher Akademischer Austauschdienst grant (to D.Q.), NAFöG Berlin grants (to D.Q. and H.H.), and "Persönliche Forschungsförderung" of the Charité-niversitätsmedizin Berlin (to M.C.B.W.).

2 Address correspondence and reprint requests to Dr. Monika C. Brunner-Weinzierl, Department of Paedriatrics, University Hospital Magdeburg, Leipziger Strasse 44, Magdeburg, 39104 Germany. E-mail address: Monika.Brunner-Weinzierl{at}med.ovgu.de

3 Abbreviations used in this paper: TD, thymus dependent; MHC II, MHC class II; tg, transgenic; DC, dendritic cell; LAT, linker for activation of T cells; KLH, keyhole limpet hemocyanin.







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