| First Author | Li SK | Year | 2015 |
| Journal | Mol Cell Biol | Volume | 35 |
| Issue | 9 | Pages | 1619-32 |
| PubMed ID | 25733685 | Mgi Jnum | J:224415 |
| Mgi Id | MGI:5662182 | Doi | 10.1128/MCB.00117-15 |
| Citation | Li SK, et al. (2015) Nfkb1 activation by the E26 transformation-specific transcription factors PU.1 and Spi-B promotes Toll-like receptor-mediated splenic B cell proliferation. Mol Cell Biol 35(9):1619-32 |
| abstractText | Generation of antibodies against T-independent and T-dependent antigens requires Toll-like receptor (TLR) engagement on B cells for efficient responses. However, the regulation of TLR expression and responses in B cells is not well understood. PU.1 and Spi-B (encoded by Sfpi1 and Spib, respectively) are transcription factors of the E26 transformation-specific (ETS) family and are important for B cell development and function. It was found that B cells from mice knocked out for Spi-B and heterozygous for PU.1 (Sfpi1(+/-) Spib(-/-) [PUB] mice) proliferated poorly in response to TLR ligands compared to wild-type (WT) B cells. The NF-kappaB family member p50 (encoded by Nfkb1) is required for lipopolysaccharide (LPS) responsiveness in mice. PUB B cells expressed reduced Nfkb1 mRNA transcripts and p50 protein. The Nfkb1 promoter was regulated directly by PU.1 and Spi-B, as shown by reporter assays and chromatin immunoprecipitation analysis. Occupancy of the Nfkb1 promoter by PU.1 was reduced in PUB B cells compared to that in WT B cells. Finally, infection of PUB B cells with a retroviral vector encoding p50 substantially restored proliferation in response to LPS. We conclude that Nfkb1 transcriptional activation by PU.1 and Spi-B promotes TLR-mediated B cell proliferation. |
