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首页> 外文期刊>EBioMedicine >HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection
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HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection

机译：HIV特异性B细胞频率与自然控制HIV感染患者的中和广度相关

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HIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT. ECs preserved their memory B cell compartments and in contrast to treated patients, maintained detectable HIV-specific memory B cell responses. All ECs presented IgG1+ HIV-specific memory B cells but some individuals also preserved IgG2+ or IgG3+ responses. Importantly, we also analyzed the capacity of sera from ECs to neutralize a panel of HIV strains including transmitted/founder virus. 29% and 21% of HLA-B*57+ and HLA-B*57- ECs, respectively, neutralized at least 40% of the viral strains tested. Remarkably, in HLA-B*57+ ECs the frequency of HIV-Env-specific memory B cells correlated positively with the neutralization breadth suggesting that preservation of HIV-specific memory B cells might contribute to the neutralizing responses in these patients.
机译：已从高病毒血症患者中分离出了HIV特异性的广泛中和抗体（bnAb），也从抑制HIV-1复制的HIV控制器中分离出了它们。在这些精英控制器（EC）中，多个参数有助于抑制病毒，包括遗传因素和免疫反应。定义与bnAb的产生相关的免疫相关性可能有助于设计有效的免疫疗法。在这项研究中，在经治疗的HIV感染者和HIV阴性个体中，对于HLA-B * 57保护性等位基因阳性或阴性的EC，我们使用流式细胞仪和ELISPOT来表征记忆B细胞区室和HIV特异性记忆B细胞反应。 EC保留了其记忆B细胞区室，与接受治疗的患者相反，它们维持了可检测到的HIV特异性记忆B细胞反应。所有EC均呈现IgG1 + HIV特异性记忆B细胞，但一些个体也保留了IgG2 +或IgG3 +反应。重要的是，我们还分析了EC血清中和一系列HIV病毒株的能力，包括传播/基础病毒。 HLA-B * 57 +和HLA-B * 57- EC分别有29％和21％中和了至少40％的病毒株。值得注意的是，在HLA-B * 57 + EC中，HIV-Env特异性记忆B细胞的频率与中和广度呈正相关，这表明，保留HIV特异性记忆B细胞可能有助于这些患者的中和反应。

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