Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals
Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals
复制标题
DOI：
10.1084/jem.20072683
复制
发表时间：
2008-08-04
影响因子：
15.3
通讯作者：
Fauci, Anthony S.
中科院分区：
文献类型：
--
作者：
Moir, Susan;Ho, Jason;Fauci, Anthony S.
人类免疫缺陷病毒(HIV)疾病通过尚不清楚的机制导致B细胞和抗体反应受损。人类扁桃体组织中一个独特的记忆B细胞亚群(CD20(Hi)/CD27(Lo)/CD21(Lo))最近被抑制受体Fc受体样蛋白4(FCRL4)的表达所定义。在这项研究中，我们描述了HIV病毒携带者血液中类似的B细胞亚群。HIV病毒携带者B细胞表面FCRL4表达高于HIV携带者和HIV阴性者。与典型记忆表型(CD27(+))或幼稚(CD27(-)/CD21(Hi))B细胞相比，CD20(Hi)/CD27(Lo)/CD21(Lo)组织样记忆表型B细胞更富集。组织样记忆B细胞表达归巢和抑制受体的模式，类似于抗原特异性T细胞耗竭的模式。组织样记忆B细胞对B细胞刺激的反应较弱，这与多种抑制性受体的高水平表达相一致。与经典的记忆B细胞相比，组织样细胞中免疫球蛋白的多样性和复制历史较低，这与过早耗竭的情况一致。值得注意的是，HIV特异性反应在这些耗尽的组织状记忆B细胞中丰富，而总免疫球蛋白和流感特异性反应在经典记忆B细胞中丰富。这些数据表明，与艾滋病毒相关的B细胞过早耗尽可能是感染者对艾滋病毒抗体反应差的原因之一。
Human immunodeficiency virus (HIV) disease leads to impaired B cell and antibody responses through mechanisms that remain poorly defined. A unique memory B cell subpopulation (CD20(hi)/CD27(lo)/CD21(lo)) in human tonsillar tissues was recently defined by the expression of the inhibitory receptor Fc-receptor-like-4 (FCRL4). In this study, we describe a similar B cell subpopulation in the blood of HIV-viremic individuals. FCRL4 expression was increased on B cells of HIV-viremic compared with HIV-aviremic and HIV-negative individuals. It was enriched on B cells with a tissuelike memory phenotype ( CD20(hi)/CD27(lo)/CD21(lo)) when compared with B cells with a classical memory (CD27(+)) or naive (CD27(-)/CD21(hi)) B cell phenotype. Tissuelike memory B cells expressed patterns of homing and inhibitory receptors similar to those described for antigen-specific T cell exhaustion. The tissuelike memory B cells proliferated poorly in response to B cell stimuli, which is consistent with high-level expression of multiple inhibitory receptors. Immunoglobulin diversities and replication histories were lower in tissuelike, compared with classical, memory B cells, which is consistent with premature exhaustion. Strikingly, HIV-specific responses were enriched in these exhausted tissuelike memory B cells, whereas total immunoglobulin and influenza-specific responses were enriched in classical memory B cells. These data suggest that HIV-associated premature exhaustion of B cells may contribute to poor antibody responses against HIV in infected individuals.