title: Cutting Edge: The Transcription Factor Sox2 Regulates AID Expression in Class-Switched B Cells.
abstract: IgH class switch recombination (CSR) occurs through the deliberate introduction of activation-induced cytidine deaminase (AID)-instigated DNA double-strand breaks into theIgHloci. Because double-strand breaks are generally highly toxic, mechanisms that regulate AID expression are of much relevance to CSR and genomic integrity; however, effectors of such regulatory processes are still poorly understood. In this article, we show that the transcription factor sex determining region Y-box 2 (Sox2) is expressed in activated B cells, but almost exclusively in those that have undergone CSR. We demonstrate that enforced expression of Sox2 in splenic B cells severely inhibits AID expression and CSR, whereas deletion of Sox2 increases the frequency ofIgH:c-Myctranslocations. These results suggest that Sox2 may regulate AID expression in class-switched B cells to suppress genomic instability associated with CSR.
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021; and.|Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: DiMenna
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021; and.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Yen
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021; and.
authors.forename: Laura
authors.initials: L
authors.lastname: Nicolas
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021; and.
authors.forename: Rahul
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021; and.
authors.forename: Zara N
authors.identifier: 0000-0003-1057-3729
authors.initials: ZN
authors.lastname: Saldanha
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021; and chaudhuj@mskcc.org.|Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065.
authors.forename: Jayanta
authors.identifier: 0000-0002-3838-0075
authors.initials: J
authors.lastname: Chaudhuri
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D016259:Genes, myc / Q000235:genetics*; D042822:Genomic Instability; D007134:Immunoglobulin Switch Region; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology*; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase