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Updated: Jan 21, 2026

Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
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Class-Switch Recombination Occurs Infrequently in Germinal Centers.

Jonathan A Roco1, Luka Mesin2, Sebastian C Binder3

  • 1Department of Immunology and Infectious Disease and Centre for Personalised Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra ACT 0200, Australia.

Immunity
|August 4, 2019
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Class-switch recombination (CSR) occurs before germinal center (GC) formation, challenging the view of GCs as the primary site for this process. Our findings reveal IgM-dominated GCs, indicating CSR primarily happens earlier in B cell development.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Class-switch recombination (CSR) is crucial for adaptive immunity, tailoring antibody responses to pathogens.
  • CSR dysregulation is linked to autoimmune diseases and B cell lymphomas.
  • The precise timing and location of CSR, particularly in relation to germinal centers (GCs), remain incompletely understood.

Purpose of the Study:

  • To investigate the temporal and spatial relationship between CSR and germinal center B cell differentiation.
  • To determine if CSR is a hallmark event within germinal centers or occurs earlier in B cell development.

Main Methods:

  • Utilized multiple experimental approaches to track CSR events.
  • Analyzed B cell populations from secondary lymphoid organs.
  • Constructed phylogenetic trees of germinal center B cell receptors (BCRs).

Main Results:

  • CSR is initiated prior to the differentiation of B cells into GC B cells or plasmablasts.
  • CSR is significantly diminished within established germinal centers.
  • Phylogenetic analysis indicates most CSR events precede somatic hypermutation.
  • Identified the presence of IgM-dominated germinal centers.

Conclusions:

  • CSR is largely completed before B cells enter the germinal center stage.
  • Germinal centers are not the primary site for the majority of CSR events.
  • The discovery of IgM-dominated GCs challenges existing models of B cell maturation and antibody diversification.