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Long-lived plasma cells (PCs) develop in germinal centers (GCs) by the differentiation of affinity matured B cells. Antibody affinity maturation involves iterative rounds of somatic hypermutation in dark zones (DZs) and selection in light zones (LZs), however the details of where, when and how PC commitment occurs are not well-understood. Fate bifurcation at the time of selection is one possibility, with the very highest affinity GC B cells differentiating as an alternative to DZ re-entry. However, how this model fits with a need to also retain these clones in the response is not clear. Here, we show that subsets of bona fide DZ cells express the plasma cell master regulator Blimp-1 at low levels during periods of proliferation. Ex vivo culture experiments demonstrate that these cells are not yet committed to plasma cell differentiation but that they may be sensitized to go down that route. Contrary to models in which T cells directly select GC B cells to begin expressing Blimp-1, we found that expression of this transcriptional regulator occurred even when follicular helper T cells were ablated. We speculate that Blimp-1 may be induced during proliferation in the DZ, and that as such single selected cells might give rise to both GC and post-GC progeny.

Original publication

DOI

10.3389/fimmu.2018.03106

Type

Journal article

Journal

Frontiers in immunology

Publication Date

01/2018

Volume

9

Addresses

MRC Human Immunology Unit, Nuffield Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.

Keywords

Germinal Center, B-Lymphocytes, Plasma Cells, Animals, Mice, Knockout, Mice, Gene Expression Profiling, Immunophenotyping, Lymphocyte Activation, Cell Differentiation, Gene Expression Regulation, Immunity, Humoral, Single-Cell Analysis, Transcriptome, Clonal Evolution, Biomarkers, Positive Regulatory Domain I-Binding Factor 1