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Increased Numbers of B-1 Cells and Enhanced Responses against TI-2 Antigen in Mice Lacking APS, an Adaptor Molecule Containing PH and SH2 Domains

Division of Immunology, Department of Microbiology and Immunology,¹ Laboratory of Gene Expression and Regulation, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan²

Received 22 August 2003/ Returned for modification 11 November 2003/ Accepted 10 December 2003

APS (adaptor molecule containing PH and SH2 domains) is an intracellular adaptor protein that forms an adaptor family along with Lnk and SH2-B. While experiments using cultured cell lines have demonstrated that APS is phosphorylated in response to various stimuli, its in vivo functions remain unclear. We attempted to determine the physiological roles of APS by generating APS-deficient (APS^-/-) mice. APS^-/- mice were viable and fertile and showed no abnormalities or growth retardation. Immunologically, APS^-/- mice showed normal development and distribution of lymphocytes and myeloid cells, except for increased numbers of B-1 cells in the peritoneal cavity. APS^-/- mice exhibited an enhanced humoral immune response against trinitrophenol-Ficoll, a thymus-independent type 2 antigen, while APS^-/- B-2 cells exhibited normal proliferative responses and tyrosine phosphorylation of intracellular proteins upon B-cell receptor (BCR) cross-linking. APS colocalized with filamentous actin (F-actin) accumulated during the capping of BCRs in APS-transgenic B cells. After BCR stimulation, F-actin contents were lower in APS^-/- B-1 cells than in wild-type B-1 cells. Our results indicate that APS might have a novel regulatory role in actin reorganization and control of B-1 cell compartment size.

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