B-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection.
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.
Huang
Kuan-Hsiang G
KH
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.
Bonsall
David
D
Katzourakis
Aris
A
Thomson
Emma C
EC
Fidler
Sarah J
SJ
Main
Janice
J
Muir
David
D
Weber
Jonathan N
JN
Frater
Alexander J
AJ
Phillips
Rodney E
RE
Pybus
Oliver G
OG
Goulder
Philip J R
PJ
McClure
Myra O
MO
Cooke
Graham S
GS
Klenerman
Paul
P
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
D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing; D000069283:Rituximab; D007371:Interferon-gamma