TY - JOUR
T1 - Class-switch recombination occurs infrequently in germinal centers
AU - Roco, Jonathan
AU - Mesin, Luka
AU - Binder, Sebastian C
AU - Nefzger, Christian
AU - Gonzalez-Figueroa, Paula
AU - Canete, Pablo F
AU - Ellyard, Julia
AU - Shen, Qian
AU - Robert, Philippe A
AU - Cappello, Jean
AU - Vohra, Harpreet
AU - Zhang, Yang
AU - Nowasad, Carla R
AU - Schiepers, Arien
AU - Corcoran, Lynn M
AU - Toellner, Kai
AU - Polo, Jose M
AU - Meyer-Hermann, Michael
AU - Victora, Gabriel D
AU - Vinuesa, Carola G
PY - 2019/8/20
Y1 - 2019/8/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85070659620&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2019.07.001
DO - 10.1016/j.immuni.2019.07.001
M3 - Article
C2 - 31375460
SN - 1074-7613
VL - 51
SP - 337-350.e7
JO - Immunity
JF - Immunity
IS - 2
ER -