Redundant role of the Syk protein tyrosine kinase in mouse NK cell differentiation

Syk and ZAP-70 subserve nonredundant functions in B and T lymphopoiesis. In the absence of Syk, B cell development is blocked, while T cell developmen t is arrested in the absence of ZAP-70, The receptors and the signaling mol ecules required for differentiation of NK cells are poorly characterized. H ere we investigate the role of the Syk protein tyrosine kinase in NK cell d ifferentiation. Hemopoietic chimeras were generated by reconstituting alymp hoid (B-, T-, NK-) recombinase-activating gene-2 x common cytokine receptor gamma-chain double-mutant mice with Syk(-/-) fetal liver cells. The phenot ypically mature Syk(-/-) NK cells that developed in this context were fully competent in natural cytotoxicity and in calibrating functional inhibitory receptors for MHC molecules. Syk-deficient NK cells demonstrated reduced l evels of Ab-dependent cellular cytotoxicity. Nevertheless, Syk(-/-) NK cell s could signal through NK1.1 and 2B4 activating receptors and expressed ZAP -70 protein. We conclude that the Syk protein tyrosine kinase is not essent ial for murine NK cell development, and that compensatory signaling pathway s (including those mediated through ZAP-70) may sustain most NK cell functi ons in the absence of Syk.