The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers

Dinis Calado Parente Calado, Yoshiteru Sasaki, Susana A Godinho, Alex Pellerin, Karl Köchert, Barry P Sleckman, Ignacio Moreno de Alborán, Martin Janz, Scott Rodig, Klaus Rajewsky

Research output: Contribution to journalArticlepeer-review

342 Citations (Scopus)

Abstract

Germinal centers (GCs) are sites of intense B cell proliferation and are central for T cell-dependent antibody responses. However, the role of c-Myc, a key cell-cycle regulator, in this process has been questioned. Here we identified c-Myc(+) B cell subpopulations in immature and mature GCs and found, by genetic ablation of Myc, that they had indispensable roles in the formation and maintenance of GCs. The identification of these functionally critical cellular subsets has implications for human B cell lymphomagenesis, which originates mostly from GC B cells and frequently involves MYC chromosomal translocations. As these translocations are generally dependent on transcription of the recombining partner loci, the c-Myc(+) GC subpopulations may be at a particularly high risk for malignant transformation.
Original languageEnglish
Pages (from-to)1092-100
Number of pages9
JournalNature Immunology
Volume13
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Animals
  • Genetic Loci
  • B-Lymphocyte Subsets
  • Green Fluorescent Proteins
  • Mice
  • Mice, Transgenic
  • B-Lymphocytes
  • Cell Proliferation
  • Translocation, Genetic
  • Proto-Oncogene Proteins c-myc
  • Gene Deletion
  • Germinal Center
  • Genes, Reporter
  • Gene Expression Regulation
  • Cell Cycle
  • Lymphoma
  • Signal Transduction
  • Cell Transformation, Neoplastic
  • T-Lymphocytes

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