Decreased survival of B cells of HIV-viremic patients mediated by altered expression of receptors of the TNF superfamily.
Decreased survival of B cells of HIV-viremic patients mediated by altered expression of receptors of the TNF superfamily.
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DOI：
10.1084/jem.20032236
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发表时间：
2004-09-06
期刊：
影响因子：
--
通讯作者：
Fauci AS
中科院分区：
文献类型：
--
作者：
Moir S;Malaspina A;Pickeral OK;Donoghue ET;Vasquez J;Miller NJ;Krishnan SR;Planta MA;Turney JF;Justement JS;Kottilil S;Dybul M;Mican JM;Kovacs C;Chun TW;Birse CE;Fauci AS
人类免疫缺陷病毒(HIV)感染通过仍然难以捉摸的机制导致B细胞的大量扰动。我们进行了DNA微阵列、表型和功能分析，试图阐明与正在进行的HIV复制相关的B细胞干扰的机制。HIV病毒携带者与HIV携带者和HIV阴性者相比，有42个基因表达上调，其中大部分是干扰素刺激或与终末分化相关的基因。流式细胞术证实了这些增加，并表明CD21low B细胞，在HIV病毒携带者中增强，是这些变化的主要原因。肿瘤坏死因子(TNFSF)超家族受体CD95的表达增加与CD21low B细胞对CD95介导的凋亡的易感性增加相关，而CD21low B细胞的凋亡又与HIV血浆病毒血症相关。CD21low B细胞表面弱的B淋巴细胞刺激因子受体(BLyS)受体BCMA的表达增加，伴随着更强大的BLyS受体BAFF-R表达的降低，从而导致BLyS结合减少和BLyS介导的生存。这些发现表明，与干扰素刺激和终末分化相关的基因在HIV病毒感染者的B细胞中的表达改变导致细胞死亡的倾向增加，这可能对B细胞对抗原刺激的反应性有实质性的有害影响。
Human immunodeficiency virus (HIV) infection leads to numerous perturbations of B cells through mechanisms that remain elusive. We performed DNA microarray, phenotypic, and functional analyses in an effort to elucidate mechanisms of B cell perturbation associated with ongoing HIV replication. 42 genes were up-regulated in B cells of HIV-viremic patients when compared with HIV-aviremic and HIV-negative patients, the majority of which were interferon (IFN)-stimulated or associated with terminal differentiation. Flow cytometry confirmed these increases and indicated that CD21low B cells, enhanced in HIV-viremic patients, were largely responsible for the changes. Increased expression of the tumor necrosis factor (TNF) superfamily (TNFSF) receptor CD95 correlated with increased susceptibility to CD95-mediated apoptosis of CD21low B cells, which, in turn, correlated with HIV plasma viremia. Increased expression of BCMA, a weak TNFSF receptor for B lymphocyte stimulator (BLyS), on CD21low B cells was associated with a concomitant reduction in the expression of the more potent BLyS receptor, BAFF-R, that resulted in reduced BLyS binding and BLyS-mediated survival. These findings demonstrate that altered expression of genes associated with IFN stimulation and terminal differentiation in B cells of HIV-viremic patients lead to an increased propensity to cell death, which may have substantial deleterious effects on B cell responsiveness to antigenic stimulation.
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影响因子：
4.4
作者：
Hauser, AE;Debes, GF;Manz, RA
通讯作者：
Manz, RA
影响因子：
4.6
作者：
Illges, H;Braun, M;Melchers, I
通讯作者：
Melchers, I
DOI：
10.1097/00126334-200212150-00003
发表时间：
2002-12-15
影响因子：
3.6
作者：
Jacobson, MA;Khayam-Bashi, H;Ng, V
通讯作者：
Ng, V
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
20.3
作者：
De Milito, A;Nilsson, A;Chiodi, F
通讯作者：
Chiodi, F