The goal of this report was to propose a model, wherein synergy between the B-cell antigen receptor (BCR) and toll-like receptor (TLR) signaling is involved in the selection of the B-cell precursors of HIV-1 broadly neutralizing antibodies (bnAbs) with long heavy chain complementarity determining regions 3, from immature/transitional B cells. The model predicts the involvement of Ab/HIV-1 complexes in a way that Ab from the complex binds both BCRs and HIV-1, while on internalization of HIV-1 TLR ligands such as CpG motifs interacts with TLR9. The result of BCR and TLR9 orchestrated signaling is a formation of somatically mutated memory B cells potential precursors of bnAbs. Generated memory B cells continuously exposed to different Ab/HIV-1 complexes can elicit specific bnAb by stochastic somatic hypermutation rather than in the Darwinian process. This new view of the interaction between Ab/HIV-1 complexes and immune system, leading to affinity maturation of the bnAbs in the absence of nominal HIV-1 antigen and BCR interaction, may have implication for the vaccine designed and passive immunization.

中文翻译：

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广泛中和HIV-1抗体选择和抗体亲和力成熟的潜在B细胞前体模型。

本报告的目的是提出一个模型，其中B细胞抗原受体（BCR）和Toll样受体（TLR）信号传导之间的协同作用涉及HIV-1广泛中和抗体的B细胞前体的选择（bnAbs）具有长的重链互补决定区3，来自未成熟/过渡性B细胞。该模型以复合物中的Ab结合BCR和HIV-1的方式预测了Ab / HIV-1复合物的参与，而在HIV-1 TLR配体（例如CpG基序）的内在化过程中与TLR9相互作用。BCR和TLR9协调的信号转导的结果是体细胞突变的记忆B细胞bnAbs潜在前体的形成。连续暴露于不同Ab / HIV-1复合物的生成的记忆B细胞可以通过随机体细胞超突变而不是达尔文过程来引发特定的bnAb。