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Address Correspondence to: Jeremy M. Boss, Ph.D., Telephone: 404-727-5973, jmboss@emory.edu

The first two authors contributed equally to this work

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Research Funding:

This work was supported by NIH grants R56AI3400 and R01AI34000 to JMB; HHSN266200700006C to IS and DGK and R01A1030048 and U19A1091493 to RA.

ZBTB32 is an early repressor of the class II transactivator and MHC class II gene expression during B cell differentiation to plasma cells

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Journal Title:

Journal of Immunology

Volume:

Volume 189, Number 5

Publisher:

, Pages 2393-2403

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The MHC class II transactivator (CIITA) and MHC class II expression is silenced during the differentiation of B cells to plasma cells. When B cell differentiation is carried out ex vivo, CIITA silencing occurs rapidly but the factors contributing to this event are not known. ZBTB32, also known as repressor of GATA3, was identified as an early repressor of CIITA in an ex vivo plasma cell differentiation model. ZBTB32 activity occurred at a time when Blimp-1, the regulator of plasma cell fate and suppressor of CIITA, was minimally induced. Ectopic expression of ZBTB32 suppressed CIITA and I-A gene expression in B cells. ShRNA depletion of ZBTB32 in a plasma cell line resulted in reexpression of CIITA and I-A. Compared to conditional Blimp-1 knock out and wild-type B cells, B cells from ZBTB32/ROG-knock out mice displayed delayed kinetics in silencing CIITA during ex vivo plasma cell differentiation. ZBTB32 was found to bind to the CIITA gene, suggesting that ZBTB32 directly regulates CIITA. Lastly, ZBTB32 and Blimp-1 coimmunoprecipitated, suggesting that the two repressors may ultimately function together to silence CIITA expression. These results introduce ZBTB32 as a novel regulator of MHC-II gene expression and a potential regulatory partner of Blimp-1 in repressing gene expression.

Copyright information:

© 2012 by The American Association of Immunologists, Inc.

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