Stimulatory and inhibitory influences of human immunodeficiency virus on normal B lymphocytes.
Stimulatory and inhibitory influences of human immunodeficiency virus on normal B lymphocytes.
复制标题
人类免疫缺陷病毒对正常 B 淋巴细胞的刺激和抑制影响。
DOI：
10.1073/pnas.83.23.9124
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发表时间：
1986
影响因子：
11.1
通讯作者：
Saxinger,C
中科院分区：
文献类型：
--
作者：
Pahwa,S;Pahwa,R;Good,RA;Gallo,RC;Saxinger,C
B淋巴细胞功能障碍是获得性免疫缺陷综合征（AIDS）和AIDS相关综合征的特征。本研究的目的是进一步研究人类免疫缺陷病毒（HIV;以前称为人类T淋巴细胞病毒III型或淋巴结病相关病毒，HTLV-III/LAV）对正常人B淋巴细胞的影响。由密度梯度离心纯化的HIV制备的未分级蛋白质制剂先前显示可诱导正常人B淋巴细胞分化为免疫球蛋白分泌细胞。在本分析中，这种B淋巴细胞反应在培养开始后第6或7天达到峰值，并且发现其不依赖于对单核细胞的需求，而是需要T细胞。在纯化的B细胞培养物中加入接触过HIV抗原的T细胞也能引起反应。蛋白质合成抑制剂（嘌呤霉素和放线菌酮）废除的反应。与其刺激作用相反，相同的病毒制剂先前显示出抑制多克隆反应，所述多克隆反应通常在外周血淋巴细胞培养物中由T依赖性刺激（美洲商陆有丝分裂原）和T非依赖性刺激（爱泼斯坦-巴尔病毒）引起。目前的研究表明，本文研究的HIV抗原的抑制作用主要针对B淋巴细胞。T淋巴细胞在HIV抗原介导的抑制作用中的作用虽然得到证实，但不能最终确定为一种重要途径。这些发现阐明了HIV组分对人B淋巴细胞产生刺激和抑制作用的机制，从而导致这些细胞在HIV感染中的功能障碍。
B-lymphocyte dysfunction is a characteristic feature of the acquired immunodeficiency syndrome (AIDS) and of the AIDS-related complex. The aim of the present study was to further examine the influences exercised by the human immunodeficiency virus (HIV; formerly called human T-lymphotropic virus type III or lymphadenopathy-associated virus, HTLV-III/LAV) on normal human B lymphocytes. An unfractionated protein preparation, made from HIV purified by density gradient centrifugation, was previously shown to induce differentiation of normal human B lymphocytes into immunoglobulin-secreting cells. In the present analyses, this B-lymphocyte response peaked on day 6 or 7 after culture initiation and was found to be independent of the requirement for monocytes but to require T cells. Responses could also be elicited in cultures of purified B cells by the addition of T cells that had been exposed to HIV antigen. Inhibitors of protein synthesis (puromycin and cycloheximide) abrogated the responses. In contrast to its stimulatory effects, the same virus preparation was previously shown to inhibit polyclonal responses that are normally elicited in peripheral blood lymphocyte cultures by a T-dependent stimulus (pokeweed mitogen) and T-independent stimulus (Epstein-Barr virus). The present studies suggest that the inhibitory effects of the HIV antigen studied herein are targeted primarily at the B lymphocytes. The role of T lymphocytes in the HIV antigen-mediated inhibitory effects, although demonstrated, could not be conclusively established as an essential pathway. These findings elucidate mechanisms by which components of HIV exert stimulatory as well as inhibitory effects on human B lymphocytes and thereby lead to the dysfunction of these cells in HIV infection.