A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin 5

A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin 5

^*Departments of Immunology and ^†Oncology, Institute of Medical Science, University of Tokyo, 4–6-1 Shirokanedai, Minato-ku, Tokyo 108 Japan; ^‡Department of Morphogenesis, Kumamoto University School of Medicine, Kumamoto 860, Japan; and ^§Department of Immunology, Saga Medical School, Saga 849, Japan

Communicated by Tadamitsu Kishimoto, Osaka University Medical School, Suita-City, Japan (received for review April 13, 1997)

Abstract

CD38 ligation on mouse B cells by CS/2, an anti-mouse CD38 mAb, induced proliferation, interleukin 5 (IL-5) receptor α chain expression, and tyrosine phosphorylation of Bruton tyrosine kinase (Btk) from wild-type, but not from X chromosome-linked, immunodeficient mice. B cells from fyn-deficient (Fyn^−/−) and lyn-deficient (Lyn^−/−) mice showed an impaired response to mAb CS/2 for proliferation and IL-5 receptor α 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 was severely impaired in B cells from Lyn^−/− and Fyn/Lyn^−/− mice. CD38 expression on B cells from three mutant strains was comparable to that 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 triggering after CD38 ligation. Lyn is upstream of Btk activation in the CD38 signaling. Stimulation of B cells with IL-5 together with CD38 ligation induces not only IgM but also IgG1 secretion. Analysis of the synergistic effects of IL-5 and CD38 ligation on IgG1 secretion revealed 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.

Footnotes

↵ ¶ To whom reprint requests should be addressed. e-mail: takatsuk{at}ims.u-tokyo.ac.jp.
ABBREVIATIONS:

IL-5,

interleukin 5;

LPS,

lipopolysaccharide;

Lyn−/−,

lyn-deficient;

Fyn−/−,

fyn-deficient;

Fyn/Lyn−/−,

fyn and lyn double- deficient;

Btk,

Bruton tyrosine kinase