TitleLineage-specific functions of Bcl-6 in immunity and inflammation are mediated by distinct biochemical mechanisms.
Publication TypeJournal Article
Year of Publication2013
AuthorsHuang, ChuanXin, Hatzi Katerina, and Melnick Ari
JournalNat Immunol
Volume14
Issue4
Pagination380-8
Date Published2013 Apr
ISSN1529-2916
KeywordsAnimals, Antibody Affinity, B-Lymphocytes, Cell Lineage, Cell Survival, Chemokines, Female, Germinal Center, Immunoglobulins, Inflammation, Lymphocyte Activation, Macrophages, Mice, Mice, Knockout, Phenotype, Proto-Oncogene Proteins c-bcl-6, T-Lymphocyte Subsets, T-Lymphocytes, Helper-Inducer
Abstract

<p>The transcription factor Bcl-6 orchestrates germinal center (GC) reactions through its actions in B cells and T cells and regulates inflammatory signaling in macrophages. Here we found that genetic replacement with mutated Bcl6 encoding Bcl-6 that cannot bind corepressors to its BTB domain resulted in disruption of the formation of GCs and affinity maturation of immunoglobulins due to a defect in the proliferation and survival of B cells. In contrast, loss of function of the BTB domain had no effect on the differentiation and function of follicular helper T cells or that of other helper T cell subsets. Bcl6-null mice had a lethal inflammatory phenotype, whereas mice with a mutant BTB domain had normal healthy lives with no inflammation. The repression of inflammatory responses by Bcl-6 in macrophages was accordingly independent of the repressor function of the BTB domain. Bcl-6 thus mediates its actions through lineage-specific biochemical functions.</p>

DOI10.1038/ni.2543
Alternate JournalNat Immunol
PubMed ID23455674
PubMed Central IDPMC3604075
Grant ListR01 CA104348 / CA / NCI NIH HHS / United States
R01 CA143032 / CA / NCI NIH HHS / United States
R01 104348 / / PHS HHS / United States