Class-Switch Recombination Occurs Infrequently in Germinal Centers.

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.

journal_name

Immunity

journal_title

Immunity

authors

Roco JA,Mesin L,Binder SC,Nefzger C,Gonzalez-Figueroa P,Canete PF,Ellyard J,Shen Q,Robert PA,Cappello J,Vohra H,Zhang Y,Nowosad CR,Schiepers A,Corcoran LM,Toellner KM,Polo JM,Meyer-Hermann M,Victora GD,Vinuesa CG

doi

10.1016/j.immuni.2019.07.001

subject

Has Abstract

pub_date

2019-08-20 00:00:00

pages

337-350.e7

issue

2

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(19)30317-6

journal_volume

51

pub_type

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