Syk deficiency in nonreleaser basophils.

Abstract

Peripheral blood basophils from 10% to 20% of donors fail to degranulate in response to cross-linking the high-affinity IgE receptor FcepsilonRI. The molecular mechanisms underlying the nonreleaser phenotype have not been established. Our aim was to compare the expression of FcepsilonRI-associated protein tyrosine kinases between nonreleaser and releaser basophils. With use of Western blotting we investigated Syk and Lyn protein levels in highly purified basophils from 3 anti-IgE nonreleasers and 2 releasers. We identified 3 healthy nonatopic donors whose nonreleaser basophils express FcepsilonRI normally but fail to express protein for the tyrosine kinase Syk, which is implicated in the initiation of FcepsilonRI-mediated secretion. Protein levels for the tyrosine kinase Lyn are somewhat reduced but not absent in nonreleaser basophils. Levels of Lyn and Syk protein are similar in B cells, eosinophils, and neutrophils from releaser and nonreleaser donors. During these studies one nonreleaser "converted" into a releaser with concomitant basophil Syk expression. The absence of detectable Syk could explain the nonreleaser phenotype of basophils from some donors.