Yeh Chen-Hao, Nojima Takuya, Kuraoka Masayuki, Kelsoe Garnett
Department of Immunology, Duke University School of Medicine, Durham, NC, 27710, USA.
Duke University Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 27710, USA.
Nat Commun. 2018 Mar 2;9(1):928. doi: 10.1038/s41467-018-03382-x.
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.
表达高亲和力抗原受体的B细胞在生发中心（GC）中具有优势，这可能是因为它们能更多地获取抗原以呈递给滤泡辅助性T细胞，并获得更好的T细胞辅助。在这种亲和力依赖性选择模型中，GC B细胞上肽/MHCII（pMHCII）复合物的密度是选择的主要决定因素。在这里，我们在嵌合小鼠中进行了实验，这些小鼠中的B细胞仅在表达MHCII的能力上有所不同（MHCII和MHCII），结果表明GC选择对pMHCII密度减半不敏感。单独来看，两种B细胞类型产生相同的体液反应；在竞争中，MHCII B细胞优先被招募到早期GC，但一旦GC建立，这种优势就不再持续。在GC反应期间，相互竞争的MHCII和MHCII GC B细胞积累突变的情况相当，亲和力成熟速率也没有差异。我们得出结论，pMHCII密度对B细胞的选择在GC建立过程中很严格，但在GC反应期间会放松。
