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

Chen-Hao Yeh, Takuya Nojima, Masayuki Kuraoka and Garnett Kelsoe ()
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Chen-Hao Yeh: Duke University School of Medicine
Takuya Nojima: Duke University School of Medicine
Masayuki Kuraoka: Duke University School of Medicine
Garnett Kelsoe: Duke University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03382-x

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