Lineage-specific functions of Bcl-6 in immunity and inflammation are mediated by distinct biochemical mechanisms Academic Article uri icon

Overview

MeSH Major

  • Cell Lineage
  • Inflammation
  • Proto-Oncogene Proteins c-bcl-6

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.

publication date

  • April 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3604075

Digital Object Identifier (DOI)

  • 10.1038/ni.2543

PubMed ID

  • 23455674

Additional Document Info

start page

  • 380

end page

  • 8

volume

  • 14

number

  • 4