CRITICAL ROLE OF LYN AND FYN FOR B-CELL RESPONSES TO CD38 LIGATION AND INTERLEUKIN-5

CD38 ligation on mouse B cells by CS/2, an anti-mouse CD38 mAb, induce d proliferation, interleukin 5 (IL-5) receptor cu chain expression, an d tyrosine phosphorylation of Bruton tyrosine kinase (Btk) from wild-t ype, but not from X chromosome-linked, immunodeficient mice. B cells f rom fyn-deficient (Fyn(-/-)) and lyn-deficient (Lyn(-/-)) mice showed an impaired response to mAb CS/2 for proliferation and IL-5 receptor a lpha chain expression, and B cells from fyn/lyn double-deficient (Fyn/ Lyn(-/-)) mice did not respond at all to mAb CS/2, The Btk activation by CD38 ligation was observed in B cells from Fyn(-/-) mice, and it wa s severely impaired in B cells from Lyn(-/-) and Fyn/Lyn(-/-) mice, CD 38 expression on B cells from three mutant strains was comparable to t hat on control B cells, We infer from these results that both Fyn and Lyn are required and that their signals are synergistic for B cell tri ggering after CD38 ligation, Lyn is upstream of Btk activation in the CD38 signaling, Stimulation of B cells with IL-5 together with CD38 li gation induces not only IgM but also IgG1 secretion. Analysis of the s ynergistic effects of IL-5 and CD38 ligation on IgG1 secretion reveale d the impaired IgG1 secretion of B cells from Lyn(-/-) and Fyn/Lyn(-/- ) mice. These data imply that Lyn is involved in B cell triggering by CD38 ligation plus IL-5 for isotype switching.