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PMID: 9294206 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 19 ·1997-09-16 ·Pages 10307-12

Yasue T, Nishizumi H, Aizawa S, Yamamoto T, Miyake K, Mizoguchi C, Uehara S, Kikuchi Y, Takatsu K

Abstract

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.

MeSH Terms
ADP-ribosyl Cyclase ADP-ribosyl Cyclase 1 Animals Antigens, CD Antigens, Differentiation/metabolism B-Lymphocytes/immunology Immunoglobulin G/biosynthesis Interleukin-5/metabolism Membrane Glycoproteins Mice Mice, Knockout NAD+ Nucleosidase/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-fyn Receptors, Interleukin/metabolism Receptors, Interleukin-5 Signal Transduction src-Family Kinases/metabolism
Chemicals
Antigens, CD Antigens, Differentiation Immunoglobulin G Interleukin-5 Membrane Glycoproteins Proto-Oncogene Proteins Receptors, Interleukin Receptors, Interleukin-5 Fyn protein, mouse Proto-Oncogene Proteins c-fyn src-Family Kinases ADP-ribosyl Cyclase Cd38 protein, mouse NAD+ Nucleosidase ADP-ribosyl Cyclase 1
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Yasue T
Department of Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108 Japan.
Nishizumi H
Aizawa S
Yamamoto T
Miyake K
Mizoguchi C
Uehara S
Kikuchi Y
Takatsu K
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.19.10307
Published
1997-09-16
Pages
10307-12
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23358
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.94.19.10307 PMC Full Text View journal details
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