Dataset Information


Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation.

ABSTRACT: 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.

PROVIDER: S-EPMC2839140 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC2950883 | BioStudies
2014-01-01 | S-EPMC4103347 | BioStudies
| S-EPMC5900439 | BioStudies
| S-EPMC2744141 | BioStudies
| S-EPMC2840041 | BioStudies
| S-EPMC8645892 | BioStudies
| S-EPMC4577851 | BioStudies
| S-EPMC3916410 | BioStudies
| S-EPMC4718598 | BioStudies
| S-EPMC5328188 | BioStudies