| First Author | Zhang X | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 12 | Pages | 5984-92 |
| PubMed ID | 24244019 | Mgi Jnum | J:207111 |
| Mgi Id | MGI:5554476 | Doi | 10.4049/jimmunol.1300611 |
| Citation | Zhang X, et al. (2013) The tumor promoter and NF-kappaB modulator Bcl-3 regulates splenic B cell development. J Immunol 191(12):5984-92 |
| abstractText | Bcl-3 is an atypical member of the family of IkappaB proteins. Unlike the classic members, Bcl-3 functions as a nuclear transcriptional cofactor that may, depending on context, promote or suppress genes via association with p50/NF-kappaB1 or p52/NF-kappaB2 homodimers. Bcl-3 is also an oncogene, because it is a partner in recurrent translocations in B cell tumors, resulting in deregulated expression. Bcl-3 functions, however, remain poorly understood. We have investigated the role of Bcl-3 in B cells and discovered a previously unknown involvement in the splenic development of these cells. Loss of Bcl-3 in B cells resulted in significantly more marginal zone (MZ) and fewer follicular (FO) B cells. Conversely, transgenic expression of Bcl-3 in B cells generated fewer MZ and more FO B cells. Both Bcl-3(-/-) FO and MZ B cells were more responsive to LPS stimulation compared with their wild-type counterparts, including increased proliferation. By contrast, Bcl-3(-/-) FO B cells were more prone to apoptosis upon BCR stimulation, also limiting their expansion. The data reveal Bcl-3 as a regulator of B cell fate determination, restricting the MZ path and favoring the FO pathway, at least in part, via increased signal-specific survival of the latter, a finding of relevance to its tumorigenic activity. |
