title: B-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection.
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 log(10) 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.
authors.affiliation: Nuffield Department of Medicine and NIHR Biomedical Research Centre, Oxford Martin School, Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, UK.
authors.forename: Kuan-Hsiang G
authors.initials: KH
authors.lastname: Huang
authors.forename: David
authors.initials: D
authors.lastname: Bonsall
authors.forename: Aris
authors.initials: A
authors.lastname: Katzourakis
authors.forename: Emma C
authors.initials: EC
authors.lastname: Thomson
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Fidler
authors.forename: Janice
authors.initials: J
authors.lastname: Main
authors.forename: David
authors.initials: D
authors.lastname: Muir
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Weber
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Frater
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Phillips
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Pybus
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Myra O
authors.initials: MO
authors.lastname: McClure
authors.forename: Graham S
authors.initials: GS
authors.lastname: Cooke
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019295:Computational Biology / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing; D000069283:Rituximab; D007371:Interferon-gamma