Cutting edge:: Genetic variation influences FcεRI-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 epsilon RI), and greater sensitivity to anaphylaxis when compared with C57BL/6 mice. Bone marrow-derived mast cells (BMMCs) fro in 129/Sv mice showed more robust degranulation upon the engagement of Fc epsilon RI. 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 bad 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 bypodegranulation, respectively. The findings demonstrate a genetic influence on the extent of a mast cell's response and identify Fyn kinase as a contributory determinant.