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* Deutsches Rheuma-Forschungszentrum, Berlin;
Klinik für Innere Medizin mit Schwerpunkt Rheumatologie und Klinischer Immunologie, Charité-Universitätsmedizin, Berlin, Germany; and
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.
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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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