The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry

Nat Immunol. 2012 Nov;13(11):1083-91. doi: 10.1038/ni.2428. Epub 2012 Sep 23.


After antigenic challenge, B cells enter the dark zone (DZ) of germinal centers (GCs) to proliferate and hypermutate their immunoglobulin genes. Mutants with greater affinity for the antigen are positively selected in the light zone (LZ) to either differentiate into plasma and memory cells or reenter the DZ. The molecular circuits that govern positive selection in the GC are not known. We show here that the GC reaction required biphasic regulation of expression of the cell-cycle regulator c-Myc that involved its transient induction during early GC commitment, its repression by Bcl-6 in DZ B cells and its reinduction in B cells selected for reentry into the DZ. Inhibition of c-Myc in vivo led to GC collapse, which indicated an essential role for c-Myc in GCs. Our results have implications for the mechanism of GC selection and the role of c-Myc in lymphomagenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Cell Cycle / genetics
  • Cell Cycle / immunology
  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / immunology
  • Gene Expression Regulation
  • Genes, Reporter
  • Genes, myc / immunology*
  • Germinal Center / immunology
  • Germinal Center / metabolism*
  • Germinal Center / pathology
  • Green Fluorescent Proteins
  • Lymphoma / genetics
  • Lymphoma / metabolism
  • Lymphoma / pathology
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-6 / genetics*
  • Proto-Oncogene Proteins c-bcl-6 / immunology
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology


  • Antigens, CD
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, Antigen, B-Cell
  • Green Fluorescent Proteins

Associated data

  • GEO/GSE38304