| First Author | Andrews SF | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 5 | Pages | 2868-78 |
| PubMed ID | 19234182 | Mgi Jnum | J:146250 |
| Mgi Id | MGI:3837088 | Doi | 10.4049/jimmunol.0802368 |
| Citation | Andrews SF, et al. (2009) Transitional B cells exhibit a B cell receptor-specific nuclear defect in gene transcription. J Immunol 182(5):2868-78 |
| abstractText | The signaling programs that enforce negative selection in early transitional (T1) B cells in response to BCR engagement remain poorly defined. We conducted a comprehensive comparison of BCR signaling in T1 vs follicular mature splenic B cells. T1, in contrast to follicular mature B cells, failed to express key NF-kappaB target genes in response to BCR engagement and exhibited a striking defect in assembly of an active transcriptional complex at the promoter of the survival and proliferative genes A1 and c-Myc. Surprisingly, and contrary to previous models, classical protein kinase C and IkappaB kinase activation, NF-kappaB nuclear translocation and DNA binding were intact in T1 B cells. Furthermore, despite a marked reduction in NFAT1 expression, differential NFAT or AP-1 activation cannot explain this transcriptional defect. Our combined findings demonstrate that T1 B cells are programmed for signal- and stage-specific 'nuclear nonresponsiveness' upon encounter with self-Ags. |
