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

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) comple...

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Detalles Bibliográficos
Autores principales: Yeh, Chen-Hao, Nojima, Takuya, Kuraoka, Masayuki, Kelsoe, Garnett
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834622/
https://www.ncbi.nlm.nih.gov/pubmed/29500348
http://dx.doi.org/10.1038/s41467-018-03382-x
Descripción
Sumario: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.