Class-switch recombination occurs infrequently in germinal centers

Research output: Contribution to journalArticle

Authors

  • Jonathan Roco
  • Luka Mesin
  • Sebastian C Binder
  • Christian Nefzger
  • Paula Gonzalez-Figueroa
  • Pablo F Canete
  • Julia Ellyard
  • Qian Shen
  • Philippe A Robert
  • Jean Cappello
  • Harpreet Vohra
  • Carla R Nowasad
  • Arien Schiepers
  • Lynn M Corcoran
  • Jose M Polo
  • Michael Meyer-Hermann
  • Gabriel D Victora
  • Carola G Vinuesa

Colleges, School and Institutes

External organisations

  • The Australian National University
  • Rockefeller University
  • Helmholtz-Centre for Infection Research
  • The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
  • University of Melbourne
  • Monash University
  • Technische Universität Braunschweig
  • Shanghai JiaoTong University

Abstract

Class-switch recombination (CSR) is a DNA recombination process that replaces the immunoglobulin (Ig) constant region for the isotype that can best protect against the pathogen. Dysregulation of CSR can cause self-reactive BCRs and B cell lymphomas; understanding the timing and location of CSR is therefore important. Although CSR commences upon T cell priming, it is generally considered a hallmark of germinal centers (GCs). Here, we have used multiple approaches to show that CSR is triggered prior to differentiation into GC B cells or plasmablasts and is greatly diminished in GCs. Despite finding a small percentage of GC B cells expressing germline transcripts, phylogenetic trees of GC BCRs from secondary lymphoid organs revealed that the vast majority of CSR events occurred prior to the onset of somatic hypermutation. As such, we have demonstrated the existence of IgM-dominated GCs, which are unlikely to occur under the assumption of ongoing switching.

Details

Original languageEnglish
Article numbere7
Pages (from-to)337-350
JournalImmunity
Volume51
Issue number2
Early online date30 Jul 2019
Publication statusPublished - 20 Aug 2019