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

• Authors: Hyesuk Yoon, Emory University; Christopher Scharer, Emory University; Parimal Majumder, Emory University; Carl W. Davis, Emory University; Royce Butler, Emory University; Wendy Zinzow-Kramer, Emory University; Ioanna Skountzou, Emory University; Dimitrios G. Koutsonanos, Emory University; Rafi Ahmed, Emory University; Rafi Ahmed, Emory University; Jeremy Boss, Emory University
• Journal Title: Journal of Immunology
• Volume: Volume 189, Number 5
• Publisher: American Association of Immunologists | 2012-09-01, Pages 2393-2403
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.4049/jimmunol.1103371
• Subjects: Biology, Microbiology; Health Sciences, Immunology

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.