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International Immunology, Vol. 11, No. 9, 1441-1449, September 1999
© 1999 Japanese Society for Immunology

Distinctive roles of Fyn and Lyn in IgD- and IgM-mediated signaling

Keisuke Horikawa1,2, Hirofumi Nishizumi1, Hisashi Umemori1, Shinichi Aizawa3, Kiyoshi Takatsu2 and Tadashi Yamamoto1

1 Departments of Oncology and
2 Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan
3 Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan

Correspondence to: T. Yamamoto

Src family kinases Fyn and Lyn associate with the B cell antigen receptor (BCR). Accumulating data show that Lyn plays important roles in BCR-mediated signaling, while the role of Fyn remains obscure. Here we dissected the role of Fyn and Lyn in BCR signaling using B cells from fyn–/–, lyn–/– and fyn/lyn double-deficient (fyn–/–lyn–/–) mice. In contrast to previous reports, fyn–/– B cells were slightly hyporeactive to both anti-IgM and anti-IgD–dextran. Although lyn–/– B cells were hyper-reactive to anti-IgM, anti-IgD-induced proliferation was impaired in lyn–/– B cells. Most of the other phenotypes of fyn–/–lyn–/– mice were similar to that of lyn–/– mice, except that proliferative responses of B cells to various stimuli, such as BCR cross-linking and lipopolysaccharide, were significantly lower in fyn–/–lyn–/– mice than in lyn–/– mice. Finally, immune responses to thymus-independent type 2 antigen were affected in these mutant mice. These observations suggest that Fyn and Lyn are involved in B cell functions, and play similar, but partly distinct, roles in BCR signaling.

Keywords: B cell receptor, B lymphocytes, knockout, signal transduction, Src family protein tyrosine kinase

Transmitting editor: S. Nishikawa


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