B-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection

Kuan-Hsiang G. Huang, David Bonsall, Aris Katzourakis, Emma C. Thomson, Sarah J. Fidler, Janice Main, David Muir, Jonathan N. Weber, Alexander J. Frater, Rodney E. Phillips, Oliver G. Pybus, Philip J.R. Goulder, Myra O. McClure, Graham S. Cooke and Paul Klenerman ()
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Kuan-Hsiang G. Huang: Oxford Martin School, Peter Medawar Building for Pathogen Research, University of Oxford
David Bonsall: Jefferiss Research laboratories, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place
Aris Katzourakis: University of Oxford
Emma C. Thomson: Jefferiss Research laboratories, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place
Sarah J. Fidler: Jefferiss Research laboratories, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place
Janice Main: Jefferiss Research laboratories, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place
David Muir: Jefferiss Research laboratories, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place
Jonathan N. Weber: Jefferiss Research laboratories, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place
Alexander J. Frater: Oxford Martin School, Peter Medawar Building for Pathogen Research, University of Oxford
Rodney E. Phillips: Oxford Martin School, Peter Medawar Building for Pathogen Research, University of Oxford
Oliver G. Pybus: University of Oxford
Philip J.R. Goulder: Oxford Martin School, Peter Medawar Building for Pathogen Research, University of Oxford
Myra O. McClure: Jefferiss Research laboratories, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place
Graham S. Cooke: Jefferiss Research laboratories, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place
Paul Klenerman: Oxford Martin School, Peter Medawar Building for Pathogen Research, University of Oxford

Nature Communications, 2010, vol. 1, issue 1, 1-7

Abstract: Abstract 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.

Date: 2010
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DOI: 10.1038/ncomms1100

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