Previous studies implicate the nonreceptor protein tyrosine kinase (PT
K) p59(fyn) in the propagation of signals from the B cell antigen rece
ptor. To elucidate the functions of this kinase, we examined B cell re
sponsiveness in mice engineered to lack the hematopoietic isoform of p
59(fyn). Remarkably, antigen receptor signaling was only modestly defe
ctive in fyn(Tnull) B cells. In contrast, signaling from the interleuk
in (IL)-5 receptor, which ordinarily provides a comitogenic stimulus w
ith antiimmunoglobulin, was completely blocked. Our results document t
he importance of p59(fynT) in IL-5 responses in B cells, and they supp
ort a general model for cytokine receptor signal transduction involvin
g the simultaneous recruitment of at least three families of PTK.