Regulation of Follicular B Cell Differentiation by the Related E26 Transformation-Specific Transcription Factors PU.1, Spi-B, and Spi-C (original) (raw)
Journal Article
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario
,
London, Ontario N6A 5C1
,
Canada
Centre for Human Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario
,
London, Ontario N6A 5C1
,
Canada
Address correspondence and reprint requests to Dr. Rodney P. DeKoter, Department of Microbiology and Immunology, Centre for Human Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada N6A 5C1. E-mail address: [email protected]
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Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario
,
London, Ontario N6A 5C1
,
Canada
Centre for Human Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario
,
London, Ontario N6A 5C1
,
Canada
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Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario
,
London, Ontario N6A 5C1
,
Canada
Centre for Human Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario
,
London, Ontario N6A 5C1
,
Canada
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Li S Xu ,
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario
,
London, Ontario N6A 5C1
,
Canada
Centre for Human Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario
,
London, Ontario N6A 5C1
,
Canada
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Department of Oncology, London Regional Cancer Program, The University of Western Ontario
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London, Ontario N6A 5C1
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Canada
Lawson Health Research Institute, The University of Western Ontario
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London, Ontario N6A 5C1
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Canada
Department of Biochemistry, The University of Western Ontario
,
London, Ontario N6A 5C1
,
Canada
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Department of Oncology, London Regional Cancer Program, The University of Western Ontario
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London, Ontario N6A 5C1
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Canada
Lawson Health Research Institute, The University of Western Ontario
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London, Ontario N6A 5C1
,
Canada
Department of Biochemistry, The University of Western Ontario
,
London, Ontario N6A 5C1
,
Canada
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Department of Biochemistry, The State University of New York at Buffalo
,
Buffalo, NY 14203
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Department of Biochemistry, The State University of New York at Buffalo
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Buffalo, NY 14203
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Accepted:
05 October 2010
Published:
15 December 2010
Cite
Rodney P DeKoter, Marc Geadah, Sonam Khoosal, Li S Xu, Gobi Thillainadesan, Joseph Torchia, Shu Shien Chin, Lee Ann Garrett-Sinha, Regulation of Follicular B Cell Differentiation by the Related E26 Transformation-Specific Transcription Factors PU.1, Spi-B, and Spi-C, The Journal of Immunology, Volume 185, Issue 12, December 2010, Pages 7374–7384, https://doi.org/10.4049/jimmunol.1001413
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Abstract
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.
Copyright © 2010 by The American Association of Immunologists, Inc.
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