Thymic stromal lymphopoietin: A cytokine that promotes the development of IgM(+) B cells in vitro and signals via a novel mechanism

A novel cytokine from a thymic stromal cell line (thymic stromal lymphopoie tin (TSLP));promotes the development of B220(+)/IgM(+) immature B cells whe n added to fetal liver cultures, long term bone marrow cultures, or bone ma rrow cells plated in semisolid medium, Because the activities of TSLP overl ap with those of IL-7 in some in vitro assays, we compared the signaling me chanisms employed by TSLP and IL-7. Proliferation of a factor-dependent pre -B cell line (NAG8/7) in response to either TSLP or IL-7 was inhibited by a nti-IL-7R alpha mAbs, suggesting that the functional TSLP receptor complex uses IL-7R alpha. In contrast, three different Abs to the common cytokine r eceptor gamma-chain had no effect on the response of these cells to TSLP, i ndicating that the functional TSLP receptor complex does not use the common cytokine receptor gamma-chain, Both cytokines induced activation of Stat5, but only IL-7 induced activation of the Janus family kinases Jak1 and Jak3 . In fact, TSLP failed to activate any of the four known Janus family kinas es, suggesting that Stat5 phosphorylation is mediated by a novel mechanism. Taken together, these data support the idea that TSLP can make unique cont ributions to B lymphopoiesis and indicate that it does so by mechanisms dis tinct from IL-7.