A Flt3- and Ras-dependent pathway primes B cell development by inducing a state of IL-7 responsiveness

N. Xi Li, Christine A. Goetz, Casey D.S. Katerndahl, Nobuo Sakaguchi, Michael A. Farrar

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Ras plays an important role in B cell development. However, the stage at which Ras governs B cell development remains unclear. Moreover, the upstream receptors and downstream effectors of Ras that govern B cell differentiation remain undefined. Using mice that express a dominant-negative form of Ras, we demonstrate that Ras-mediated signaling plays a critical role in the development of common lymphoid progenitors. This developmental block parallels that found in flt3-/- mice, suggesting that Flt3 is an important upstream activator of Ras in early B cell progenitors. Ras inhibition impaired proliferation of common lymphoid progenitors and pre-pro-B cells but not pro-B cells. Rather, Ras promotes STAT5-dependent pro-B cell differentiation by enhancing IL-7Rα levels and suppressing socs2 and socs3 expression. Our results suggest a model in which Flt3/Ras-dependent signals play a critical role in B cell development by priming early B cell progenitors for subsequent STAT5-dependent B cell differentiation.

Original languageEnglish (US)
Pages (from-to)1728-1736
Number of pages9
JournalJournal of Immunology
Volume184
Issue number4
DOIs
StatePublished - Feb 15 2010

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