A 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, induced proliferation, interleukin 5 (IL-5) receptor alpha 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 alpha 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.
Yasue
T
T
Department of Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108 Japan.
Nishizumi
H
H
Aizawa
S
S
Yamamoto
T
T
Miyake
K
K
Mizoguchi
C
C
Uehara
S
S
Kikuchi
Y
Y
Takatsu
K
K
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D015848:Interleukin-5 / Q000378:metabolism*; D008562:Membrane Glycoproteins; D051379:Mice; D018345:Mice, Knockout; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D018123:Receptors, Interleukin / Q000378:metabolism; D053649:Receptors, Interleukin-5; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1