An analysis of B cell selection mechanisms in germinal centres
An analysis of B cell selection mechanisms in germinal centres
复制标题
DOI：
10.1093/imammb/dql012
复制
发表时间：
2006-09-01
影响因子：
1.1
通讯作者：
Iber, Dagmar
中科院分区：
文献类型：
--
作者：
Meyer-Hermann, Michael E.;Maini, Philip K.;Iber, Dagmar
免疫应答过程中抗体的亲和力成熟是通过多轮体细胞高频突变以及随后对那些表达与抗原结合特性更佳的B细胞受体的B细胞进行优先选择来实现的。B细胞选择的潜在机制尚未明确。通过采用基于主体的模型，我们表明，对于生理上合理的参数值，亲和力成熟既不是由结合位点的竞争也不是由抗原的竞争所驱动——即使存在竞争性分泌抗体的情况下也是如此。在测试的机制中，发现只有对T细胞辅助的克隆竞争，或者中心细胞与滤泡树突状细胞相互作用的不应期，才能在产生实验观察到的生发中心特征并耐受初始抗原密度的大幅变化的同时实现亲和力成熟。
Affinity maturation of antibodies during immune responses is achieved by multiple rounds of somatic hypermutation and subsequent preferential selection of those B cells that express B cell receptors with improved binding characteristics for the antigen. The mechanism underlying B cell selection has not yet been defined. By employing an agent-based model, we show that for physiologically reasonable parameter values affinity maturation can be driven by competition for neither binding sites nor antigen-even in the presence of competing secreted antibodies. Within the tested mechanisms, only clonal competition for T cell help or a refractory time for the interaction of centrocytes with follicular dendritic cells is found to enable affinity maturation while generating the experimentally observed germinal centre characteristics and tolerating large variations in the initial antigen density.