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J Immunol. 2017 Feb 1;198(3):1220-1228. doi: 10.4049/jimmunol.1601560. Epub 2016 Dec 30.

Effect of Antiretroviral Therapy on the Memory and Activation Profiles of B Cells in HIV-Infected African Women.

Author information

  • 1Department of Pathology, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
  • 2Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban 4013, South Africa.
  • 3Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032; and.
  • 4Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa.
  • 5Department of Pathology, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; wendy.burgers@uct.ac.za.

Abstract

Human immunodeficiency virus infection induces a wide range of effects in B cells, including skewed memory cell differentiation, compromised B cell function, and hypergammaglobulinemia. However, data on the extent to which these B cell abnormalities can be reversed by antiretroviral therapy (ART) are limited. To investigate the effect of ART on B cells, the activation (CD86) and differentiation (IgD, CD27, and CD38) profiles of B cells were measured longitudinally in 19 HIV-infected individuals before (median, 2 mo) and after ART initiation (median, 12 mo) and compared with 19 age-matched HIV-uninfected individuals using flow cytometry. Twelve months of ART restored the typical distribution of B cell subsets, increasing the proportion of naive B cells (CD27-IgD+CD38-) and concomitantly decreasing the immature transitional (CD27-IgD+CD38+), unswitched memory (CD27+IgD+CD38-), switched memory (CD27+IgD-CD38- or CD27-IgD-CD38-), and plasmablast (CD27+IgD-CD38high) subsets. However, B cell activation was only partially normalized post-ART, with the frequency of activated B cells (CD86+CD40+) reduced compared with pre-ART levels (p = 0.0001), but remaining significantly higher compared with HIV-uninfected individuals (p = 0.0001). Interestingly, unlike for T cell activation profiles, the extent of B cell activation prior to ART did not correlate with HIV plasma viral load, but positively associated with plasma sCD14 levels (p = 0.01, r = 0.58). Overall, ART partially normalizes the skewed B cell profiles induced by HIV, with some activation persisting. Understanding the effects of HIV on B cell dysfunction and restoration following ART may provide important insights into the mechanisms of HIV pathogenesis.

PMID:
28039305
PMCID:
PMC5263028
[Available on 2017-08-01]
DOI:
10.4049/jimmunol.1601560
[PubMed - in process]
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