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Crk-Associated Substrate Lymphocyte Type Is Required for Lymphocyte Trafficking and Marginal Zone B Cell Maintenance¹

Sachiko Seo^*, Takashi Asai^*, Toshiki Saito^*, Takahiro Suzuki^*, Yasuyuki Morishita, Tetsuya Nakamoto^*, Motoshi Ichikawa^*, Go Yamamoto^*, Masahito Kawazu^*, Tetsuya Yamagata^*, Ryuichi Sakai, Kinuko Mitani, Seishi Ogawa^*, Mineo Kurokawa^2,*, Shigeru Chiba^* and Hisamaru Hirai^*

^* Department of Hematology and Oncology, Graduate School of Medicine, and Department of Pathology, Faculty of Medicine, University of Tokyo, Tokyo, Japan; Growth Factor Division, National Cancer Center Research Institute, Tokyo, Japan; and Department of Hematology, Dokkyo University School of Medicine, Tochigi, Japan

The lymphocyte-specific Cas family protein Cas-L (Crk-associated substrate lymphocyte type) has been implicated to function in lymphocyte movement, mediated mainly by integrin signaling. However, its physiological role is poorly understood. In this study we analyzed the function of Cas-L in lymphocytes using gene-targeted mice. The mutant mice showed a deficit of marginal zone B (MZB) cells and a decrease of cell number in secondary lymphoid organs. An insufficient chemotactic response and perturbed cell adhesion were observed in Cas-L-deficient lymphocytes, suggesting that the aberrant localization was responsible for the deficit of MZB cells. Moreover, we found that lymphocyte trafficking was altered in Cas-L-deficient mice, which gave a potential reason for contraction of secondary lymphoid tissues. Thus, Cas-L affects homeostasis of MZB cells and peripheral lymphoid organs, which is considered to be relevant to impaired lymphocyte migration and adhesion.

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