title: Lineage-specific functions of Bcl-6 in immunity and inflammation are mediated by distinct biochemical mechanisms.
abstract: 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.
authors: Division of Hematology and Oncology, Weill Cornell Medical College, New York, New York, USA.
authors: Chuanxin
authors: C
authors: Huang
authors: Katerina
authors: K
authors: Hatzi
authors: Ari
authors: A
authors: Melnick
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics* / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D007136:Immunoglobulins; D051560:Proto-Oncogene Proteins c-bcl-6