Cutting edge: genetic variation influences Fc epsilonRI-induced mast cell activation and allergic responses.
Mast cell responses are influenced by a diverse array of environmental factors, but little is known about the effect of genetic background. In this study, we report that 129/Sv mice had high levels of circulating IgE, increased expression of the high-affinity receptor for IgE (Fc epsilonRI), and greater sensitivity to anaphylaxis when compared with C57BL/6 mice. Bone marrow-derived mast cells (BMMCs) from 129/Sv mice showed more robust degranulation upon the engagement of Fc epsilonRI. Deficiency of the Src family kinase Lyn enhanced degranulation in 129/Sv BMMCs but inhibited this response in C57BL/6 cells. C57BL/6 lyn(-/-) BMMCs had reduced expression of the Src family kinase Fyn, and increasing its expression markedly enhanced degranulation. In human mast cells the silencing of Lyn or Fyn expression resulted in hyperdegranulation or hypodegranulation, respectively. The findings demonstrate a genetic influence on the extent of a mast cell's response and identify Fyn kinase as a contributory determinant.
Yamashita
Yumi
Y
Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Charles
Nicolas
N
Furumoto
Yasuko
Y
Odom
Sandra
S
Yamashita
Toshiyuki
T
Gilfillan
Alasdair M
AM
Constant
Stephanie
S
Bower
Molly A
MA
Ryan
John J
JJ
Rivera
Juan
J
D000818:Animals; D015550:Cell Degranulation / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014161:Transduction, Genetic; D019061:src-Family Kinases / Q000235:genetics / Q000276:immunology
C521907:Fc-epsilon receptor I beta-chain, mouse; D017455:Receptors, IgE; D007073:Immunoglobulin E; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases