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Molecular and Cellular Biology, November 2005, p. 9646-9660, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9646-9660.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Impaired Immune Responses and Prolonged Allograft Survival in Sly1 Mutant Mice

Sandra Beer,^1,2, Tanja Scheikl,^1, Bernhard Reis,^2, Norbert Hüser,¹ Klaus Pfeffer,² and Bernhard Holzmann^1*

Department of Surgery, Technische Universität München, 81675 Munich, Germany,¹ Institute of Medical Microbiology, Universität Düsseldorf, 40225 Düsseldorf, Germany²

Received 4 July 2005/ Accepted 27 July 2005

Adaptive immunity is crucial for protective host defense and the development of immunological disorders. SLY1 was recently identified as an X-chromosomal SH3 protein that is serine phosphorylated (Ser27) upon B-and T-cell receptor engagement. Here, we demonstrate that SLY1 is localized in the cytoplasm and the nucleus of immunocytes. We generated mice expressing a mutant version of SLY1 lacking Ser27 and a functional nuclear localization signal. The defective SLY1 (SLY1^d) protein is localized exclusively in the cytoplasm. B- and T-cell proliferation is attenuated and T-cell cytokine production is severely reduced. Sly1^d/d mice exhibit reduced lymphoid organ sizes, diminished marginal zone B-cell numbers, and severely impaired antibody responses against T-dependent and -independent antigens. Importantly, survival of semi-identical cardiac allografts was substantially prolonged in Sly1^d/d mice. These results define SLY1 as an essential molecular component for the full activation of adaptive immunity.

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* Corresponding author. Mailing address: Department of Surgery, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany. Phone: 49-89-4140 2033. Fax: 49-89-4140 6605. E-mail: holzmann{at}nt1.chir.med.tu-muenchen.de.

These authors contributed equally to this work.

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Molecular and Cellular Biology, November 2005, p. 9646-9660, Vol. 25, No. 21
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.21.9646-9660.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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