Class-switch recombination occurs infrequently in germinal centers
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
- 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
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.
|Early online date||30 Jul 2019|
|Publication status||Published - 20 Aug 2019|