| First Author | Li LX | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 4 | Pages | 1728-36 |
| PubMed ID | 20065110 | Mgi Jnum | J:159490 |
| Mgi Id | MGI:4443170 | Doi | 10.4049/jimmunol.0903023 |
| Citation | Li LX, et al. (2010) A Flt3- and Ras-dependent pathway primes B cell development by inducing a state of IL-7 responsiveness. J Immunol 184(4):1728-36 |
| abstractText | 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-7Ralpha 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. |
