Regulation of follicular B cell differentiation by the related E26 transformation-specific transcription factors PU.1, Spi-B, and Spi-C.
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 Eμ-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.
Department of Microbiology and Immunology, Centre for Human Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada. rdekoter@schulich.uwo.ca
Rodney P
RP
DeKoter
Marc
M
Geadah
Sonam
S
Khoosal
Li S
LS
Xu
Gobi
G
Thillainadesan
Joseph
J
Torchia
Shu Shien
SS
Chin
Lee Ann
LA
Garrett-Sinha
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D017455:Receptors, IgE; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C514177:Spi-B protein, mouse; C423918:Spic protein, mouse