title: Alternate pathways for Bcl6-mediated regulation of B cell to plasma cell differentiation.
abstract: The transcription factor Bcl6 regulates germinal center formation and differentiation of B cells into high-affinity antibody-producing plasma cells. The direct double-negative regulatory circuit between Bcl6 and Blimp-1 is well established. We now reveal alternative mechanisms for Bcl6-mediated regulation of B-cell differentiation to plasma cells and show with DT40 cells that Bcl6 directly promotes the expression of Bach2, a known suppressor of Blimp-1. Moreover, Bcl6 suppresses Blimp-1 expression through direct binding to the IRF4 gene, as well as by promoting the expression of MITF, a known suppressor of IRF4. We also provide evidence that Bcl6 is needed for the expression of AID and UNG, the indispensable proteins for somatic hypermutation and class-switch recombination, and UNG appears to be a direct Bcl6 target. Our findings reveal a complex regulatory network in which Bcl6 acts as a key element dictating the transition of DT40 B cells to plasma cells.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland. jukka.alinikula@utu.fi
authors.forename: Jukka
authors.initials: J
authors.lastname: Alinikula
authors.forename: Kalle-Pekka
authors.initials: KP
authors.lastname: Nera
authors.forename: Sini
authors.initials: S
authors.lastname: Junttila
authors.forename: Olli
authors.initials: O
authors.lastname: Lassila
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D002645:Chickens; D020869:Gene Expression Profiling; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018448:Models, Immunological; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
chemical_list: D030161:Avian Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D050835:Interferon Regulatory Factors; D051757:PAX5 Transcription Factor; D014157:Transcription Factors; C435124:IRF4 protein, Gallus gallus; D000099218:Interferon Regulatory Factor-4