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

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 ro le of Fyn and Lyn in BCR signaling using B cells from fyn(-/-), lyn(-/-) an d 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 lowe r in fyn(-/-)lyn(-/-) mice than in lyn(-/-) mice. Finally, immune responses to thymus-independent type 2 antigen were affected in these mutant mice. T hese observations suggest that Fyn and Lyn are involved in a cell functions , and play similar, but partly distinct, roles in BCR signaling.