Expression of the plasma cell transcriptional regulator Blimp-1 by dark zone germinal center B cells during periods of proliferation

Abstract

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.