| First Author | Rowland SL | Year | 2010 |
| Journal | J Exp Med | Volume | 207 |
| Issue | 3 | Pages | 607-21 |
| PubMed ID | 20176802 | Mgi Jnum | J:158819 |
| Mgi Id | MGI:4440684 | Doi | 10.1084/jem.20091673 |
| Citation | Rowland SL, et al. (2010) Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation. J Exp Med 207(3):607-21 |
| abstractText | B cell receptors (BCRs) generate tonic signals critical for B cell survival and early B cell development. To determine whether these signals also mediate the development of transitional and mature B cells, we examined B cell development using a mouse strain in which nonautoreactive immunoglobulin heavy and light chain-targeted B cells express low surface BCR levels. We found that reduced BCR expression translated into diminished tonic BCR signals that strongly impaired the development of transitional and mature B cells. Constitutive expression of Bcl-2 did not rescue the differentiation of BCR-low B cells, suggesting that this defect was not related to decreased cell survival. In contrast, activation of the Ras pathway rescued the differentiation of BCR-low immature B cells both in vitro and in vivo, whereas extracellular signal-regulated kinase (Erk) inhibition impaired the differentiation of normal immature B cells. These results strongly suggest that tonic BCR signaling mediates the differentiation of immature into transitional and mature B cells via activation of Erk, likely through a pathway requiring Ras. |
