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Immunity. 2019 Aug 20;51(2):337-350.e7. doi: 10.1016/j.immuni.2019.07.001. Epub 2019 Jul 30.

Class-Switch Recombination Occurs Infrequently in Germinal Centers.

Author information

1
Department 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.
2
Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, 10065, USA.
3
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Rebenring 56, 38106 Braunschweig, Germany.
4
Department of Anatomy and Developmental Biology and Australian Regenerative Medicine Institute, Monash University, Wellington Road, Clayton VIC 3800, Australia.
5
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
6
Molecular Immunology Division, the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville VIC 3052, Australia.
7
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Rebenring 56, 38106 Braunschweig, Germany; Institute for Biochemistry, Biotechnology, and Bioinformatics, Technische Universität Braunschweig, Braunschweig, Germany.
8
Department 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; China-Australia Centre for Personalised Immunology, Department of Rheumatology, Shanghai Renji Hospital, Shanghai JiaoTong University, Shanghai, China. Electronic address: carola.vinuesa@anu.edu.au.

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.

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