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Departments of
*
Immunology and
Biological Structure, University of Washington, Seattle, WA 98195;
Virginia Mason Research Center, Seattle, WA 98101; and
§
Merck Research Laboratories, Rahway, NJ 07065
A novel cytokine from a thymic stromal cell line (thymic stromal
lymphopoietin (TSLP)) promotes the development of
B220+/IgM+ immature B cells when added to fetal
liver cultures, long term bone marrow cultures, or bone marrow cells
plated in semisolid medium. Because the activities of TSLP overlap with
those of IL-7 in some in vitro assays, we compared the signaling
mechanisms 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 anti-IL-7R
mAbs, suggesting that the
functional TSLP receptor complex uses IL-7R. In contrast, three
different Abs to the common cytokine receptor 
-chain had no effect
on the response of these cells to TSLP, indicating that the functional
TSLP receptor complex does not use the common cytokine receptor
-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 kinases,
suggesting that Stat5 phosphorylation is mediated by a novel mechanism.
Taken together, these data support the idea that TSLP can make unique
contributions to B lymphopoiesis and indicate that it does so by
mechanisms distinct from IL-7.
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