First Author | DeKoter RP | Year | 2010 |
Journal | J Immunol | Volume | 185 |
Issue | 12 | Pages | 7374-84 |
PubMed ID | 21057087 | Mgi Jnum | J:167483 |
Mgi Id | MGI:4868337 | Doi | 10.4049/jimmunol.1001413 |
Citation | DeKoter RP, et al. (2010) Regulation of follicular B cell differentiation by the related E26 transformation-specific transcription factors PU.1, Spi-B, and Spi-C. J Immunol 185(12):7374-84 |
abstractText | Splenic B-2 cells can be divided into two major subsets: follicular (FO) and marginal zone (MZ) B cells. FO and MZ B cells are generated from immature transitional B cells. Few transcription factors have been identified that regulate FO B cell differentiation. The highly related proteins PU.1, Spi-B, and Spi-C are transcription factors of the E26-transformation-specific family and are important for B cell differentiation and function. To determine whether these proteins play a role in the differentiation of FO B cells, we performed a detailed analysis of splenic B cells in mice with inactivating mutations in the genes encoding PU.1 (Sfpi1) or Spi-B (Spib). Sfpi1(+/-) Spib(-/-) (PUB) mice had a 9-fold reduction in the frequency of CD23(+) FO B cells compared with that of wild-type mice. In contrast, PUB mice had a 2-fold increase in the frequency of MZ B cells that was confirmed by immunofluorescence staining. Expression of Spi-C in Emu-Spi-C transgenic PUB mice partially rescued frequencies of CD23(+) B cells. Gene expression analysis, in vitro reporter assays, and chromatin immunoprecipitation experiments showed that transcription of the Fcer2a gene encoding CD23 is activated by PU.1, Spi-B, and Spi-C. These results demonstrate that FO B cell differentiation is regulated by the E26-transformation-specific transcription factors PU.1, Spi-B, and Spi-C. |