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.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Avian Proteins / genetics
-
Avian Proteins / immunology*
-
Avian Proteins / metabolism
-
B-Lymphocytes / immunology*
-
B-Lymphocytes / metabolism
-
Basic-Leucine Zipper Transcription Factors / genetics
-
Basic-Leucine Zipper Transcription Factors / immunology
-
Basic-Leucine Zipper Transcription Factors / metabolism
-
Blotting, Western
-
Cell Differentiation / genetics
-
Cell Differentiation / immunology*
-
Cell Line, Tumor
-
Chickens
-
Gene Expression Profiling
-
Interferon Regulatory Factors / genetics
-
Interferon Regulatory Factors / immunology
-
Interferon Regulatory Factors / metabolism
-
Models, Immunological
-
Mutation
-
Oligonucleotide Array Sequence Analysis
-
PAX5 Transcription Factor / genetics
-
PAX5 Transcription Factor / immunology
-
PAX5 Transcription Factor / metabolism
-
Plasma Cells / immunology*
-
Plasma Cells / metabolism
-
Reverse Transcriptase Polymerase Chain Reaction
-
Signal Transduction / immunology*
-
Transcription Factors / genetics
-
Transcription Factors / immunology*
-
Transcription Factors / metabolism
Substances
-
Avian Proteins
-
Basic-Leucine Zipper Transcription Factors
-
IRF4 protein, Gallus gallus
-
Interferon Regulatory Factors
-
PAX5 Transcription Factor
-
Transcription Factors