J. Exp. Med., Volume 187, Number 8, April 20, 1998 1343-1348

BRIEF DEFINITIVE REPORT:
A Double-Edged Kinase Lyn: A Positive and Negative Regulator for Antigen Receptor-mediated Signals

By Hirofumi Nishizumi,^* Keisuke Horikawa,^* Irena Mlinaric-Rascan,^* and Tadashi Yamamoto^*

From the ^* Department of Oncology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; and the  Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan

B cells from young lyn^/ mice are hyperresponsive to anti-IgM-induced proliferation, suggesting involvement of Lyn in negative regulation of B cell antigen receptor (BCR)-mediated signaling. Here we show that tyrosine phosphorylation of FcRIIB and CD22 coreceptors, which are important for feedback suppression of BCR-induced signaling, was severely impaired in lyn^/ B cells upon their coligation with the BCR. Hypophosphorylation on tyrosine residues of these molecules resulted in failure of recruiting the tyrosine phosphatase SHP-1 and inositol phosphatase SHIP, SH2-containing potent inhibitors of BCR-induced B cell activation, to the coreceptors. Consequently, lyn^/ B cells exhibited defects in suppressing BCR-induced Ca²⁺ influx and proliferation. Thus, Lyn is critically important in tyrosine phosphorylation of the coreceptors, which is required for feedback suppression of B cell activation.

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