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BLIMP-1 mediates extinction of major histocompatibility class II transactivator expression in plasma cells

Nature Immunology volume 1, pages 526–532 (2000)Cite this article

Abstract

Class II transactivator (CIITA), a coactivator required for class II major histocompatibility complex (MHC) transcription, is expressed in B cells but extinguished in plasma cells. This report identifies B lymphocyte–induced maturation protein 1 (BLIMP-1), a transcriptional repressor that is capable of triggering plasma cell differentiation, as a developmentally regulated repressor of CIITA transcription. BLIMP-1 represses the B cell–specific promoter of the human gene that encodes CIITA (MHC2TA) in a binding site–dependent manner. Decreased CIITA correlates with increased BLIMP-1 during plasma cell differentiation in cultured cells. Ectopic expression of BLIMP-1 represses endogenous mRNA for CIITA and the CIITA targets, class II MHC, invariant chain and H2-DM (the murine equivalent of HLA-DM) in primary splenic B cells as well as 18-81 pre-B cells. Thus, the BLIMP-1 program of B cell differentiation includes loss of antigen presentation via extinction of CIITA expression.

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Figure 1: The B cell–specific promoter of MHC2TA contains a BLIMP-1–binding site.
Figure 2: Expression of BLIMP-1 in B cells represses both the MHC2TA and HLA-DRA promoters.
Figure 3: BLIMP-1 and PRD1-BF1 are functionally conserved across species.
Figure 4: B cells that express BLIMP-1 have decreased class II MHC and CIITA expression.
Figure 5: Ectopic BLIMP-1 expression in 18-81 cells decreases both endogenous CIITA RNA and surface expression of class II MHC.
Figure 6: Ectopic expression of BLIMP-1 in primary splenic B cells decreases the expression of endogenous mRNA for CIITA and CIITA target genes.
Figure 7: Model of the regulation of CIITA and Class II MHC by BLIMP-1.

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Acknowledgements

We thank S. Chen-Kiang for the system of in vitro B cell differentiation using IL-6. Supported by grants AI29564, AI41751, AI41580, NS34190 (to J. P. -Y. T.) and GM29361, AI43567 (to K. C.). J. F. P. is a postdoctoral fellow of the National Multiple Sclerosis Society (FG 1173-A-1 and FA 1374-A-2) and K. –I. L. is a fellow of the Leukemia and Lymphoma Society (5332-00).

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  1. Janet F. Piskurich

    Present address: Mercer University School of Medicine, Macon, GA, 31207, USA

  2. Janet F. Piskurich and Kuo -I. Lin: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, 27599, NC, USA

    Janet F. Piskurich, Ying Wang & Jenny P. -Y. Ting

  2. Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, 10032, NY, USA

    Kuo -I. Lin, Yi Lin & Kathryn Calame

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Correspondence to Jenny P. -Y. Ting.

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Piskurich, J., Lin, KI., Lin, Y. et al. BLIMP-1 mediates extinction of major histocompatibility class II transactivator expression in plasma cells. Nat Immunol 1, 526–532 (2000). https://doi.org/10.1038/82788

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