Distinctive roles of Fyn and Lyn in IgD- and IgM-mediated signaling.
Src family kinases Fyn and Lyn associate with the B cell antigen receptor (BCR). Accumulating data show that Lyn plays important roles in BCR-mediated signaling, while the role of Fyn remains obscure. Here we dissected the role of Fyn and Lyn in BCR signaling using B cells from fyn(-/-), lyn(-/-) and fyn/lyn double-deficient (fyn(-/-)lyn(-/-)) mice. In contrast to previous reports, fyn(-/-) B cells were slightly hyporeactive to both anti-IgM and anti-IgD-dextran. Although lyn(-/-) B cells were hyper-reactive to anti-IgM, anti-IgD-induced proliferation was impaired in lyn(-/-) B cells. Most of the other phenotypes of fyn(-/-)lyn(-/-) mice were similar to that of lyn(-/-) mice, except that proliferative responses of B cells to various stimuli, such as BCR cross-linking and lipopolysaccharide, were significantly lower in fyn(-/-)lyn(-/-) mice than in lyn(-/-) mice. Finally, immune responses to thymus-independent type 2 antigen were affected in these mutant mice. These observations suggest that Fyn and Lyn are involved in B cell functions, and play similar, but partly distinct, roles in BCR signaling.
Horikawa
K
K
Department of Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan.
Nishizumi
H
H
Umemori
H
H
Aizawa
S
S
Takatsu
K
K
Yamamoto
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology; D005260:Female; D007072:Immunoglobulin D / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases