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Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density.


ABSTRACT: B cells expressing high affinity antigen receptors are advantaged in germinal centers (GC), perhaps by increased acquisition of antigen for presentation to follicular helper T cells and improved T-cell help. In this model for affinity-dependent selection, the density of peptide/MHCII (pMHCII) complexes on GC B cells is the primary determinant of selection. Here we show in chimeric mice populated by B cells differing only in their capacity to express MHCII (MHCII+/+ and MHCII+/-) that GC selection is insensitive to halving pMHCII density. Alone, both B cell types generate identical humoral responses; in competition, MHCII+/+ B cells are preferentially recruited to early GCs but this advantage does not persist once GCs are established. During GC responses, competing MHCII+/+ and MHCII+/- GC B cells comparably accumulate mutations and have indistinguishable rates of affinity maturation. We conclude that B-cell selection by pMHCII density is stringent in the establishment of GCs, but relaxed during GC responses.

SUBMITTER: Yeh CH 

PROVIDER: S-EPMC5834622 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density.

Yeh Chen-Hao CH   Nojima Takuya T   Kuraoka Masayuki M   Kelsoe Garnett G  

Nature communications 20180302 1


B cells expressing high affinity antigen receptors are advantaged in germinal centers (GC), perhaps by increased acquisition of antigen for presentation to follicular helper T cells and improved T-cell help. In this model for affinity-dependent selection, the density of peptide/MHCII (pMHCII) complexes on GC B cells is the primary determinant of selection. Here we show in chimeric mice populated by B cells differing only in their capacity to express MHCII (MHCII<sup>+/+</sup> and MHCII<sup>+/-</  ...[more]

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