B-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection.
B-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection.
复制标题
DOI：
10.1038/ncomms1100
复制
发表时间：
2010-10-19
影响因子：
16.6
通讯作者：
Klenerman, Paul
中科院分区：
文献类型：
--
作者：
Huang, Kuan-Hsiang G.;Bonsall, David;Katzourakis, Aris;Thomson, Emma C.;Fidler, Sarah J.;Main, Janice;Muir, David;Weber, Jonathan N.;Frater, Alexander J.;Phillips, Rodney E.;Pybus, Oliver G.;Goulder, Philip J. R.;McClure, Myra O.;Cooke, Graham S.;Klenerman, Paul
HIV可以部分地被宿主免疫力所控制，理解这一点的基础可以为疫苗设计提供信息。B细胞功能在长期控制中的重要性知之甚少。研究这一点的一种方法是体内细胞耗竭。在这项研究中，我们利用一个独特的机会，调查B细胞在艾滋病毒感染患者的作用。在此研究的HIV-1+患者未服用抗逆转录病毒药物，并通过使用利妥昔单抗清除CD 20 + B细胞治疗先前存在的低度淋巴浆细胞样淋巴瘤。我们证明，B细胞耗竭导致自体中和抗体（NAb）反应下降，HIV-1血浆病毒载量（pVL）上升1.7 log 10。NAb的恢复导致pVL下降。HIV-1序列多样化，随后选择NAb抗性突变体。这些数据表明，B细胞功能可以有助于长期控制pVL，NAb在控制慢性HIV-1感染方面可能比以前怀疑的更重要。 HIV感染可以部分地由宿主免疫系统调节;然而，B细胞是否有助于这种反应尚不清楚。Huang等人表明，B细胞的瞬时消耗可导致HIV病毒载量的增加，这表明这些免疫细胞确实参与HIV感染的控制。
HIV can be partially contained by host immunity and understanding the basis of this may inform vaccine design. The importance of B-cell function in long-term control is poorly understood. One method of investigating this is in vivo cellular depletion. In this study, we take advantage of a unique opportunity to investigate the role of B cells in an HIV-infected patient. The HIV-1+ patient studied here was not taking antiretroviral drugs and was treated for pre-existing low-grade lymphoplasmacytoid lymphoma by depletion of CD20+ B cells using rituximab. We demonstrate that B-cell depletion results in a decline in autologous neutralizing antibody (NAb) responses and a 1.7 log10 rise in HIV-1 plasma viral load (pVL). The recovery of NAbs results in a decline in pVL. The HIV-1 sequences diversify and NAb-resistant mutants are subsequently selected. These data suggest that B-cell function can contribute to the long-term control of pVL, and that NAbs may be more important in controlling chronic HIV-1 infection than previously suspected. HIV infection can be partially regulated by the host immune system; however whether B cells contribute to this response is unclear. Huang et al. show that transient depletion of B cells can result in an increase in HIV viral load suggesting that these immune cells do participate in the control of HIV infection.
登录
查看更多内容
影响因子：
5.4
作者：
Duenas-Decamp, Maria Jose;Peters, Paul J.;Clapham, Paul R.
通讯作者：
Clapham, Paul R.
影响因子：
56.9
作者：
BURTON, DR;PYATI, J;BARBAS, CF
通讯作者：
BARBAS, CF
影响因子：
5.4
作者：
Dorfman, T;Popova, E;Göttlinger, HG
通讯作者：
Göttlinger, HG
影响因子：
168.9
作者：
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
通讯作者：
Robertson, Michael N.
影响因子：
9.8
作者：
Drummond AJ;Ho SY;Phillips MJ;Rambaut A
通讯作者：
Rambaut A