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The journal of immunology : official journal of the American Association of Immunologists v.198 no.3, 2017년, pp.1220 - 1228   SCI SCIE
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Effect of Antiretroviral Therapy on the Memory and Activation Profiles of B Cells in HIV-Infected African Women

Tanko, Ramla F. ; Soares, Andreia P. ; ; ller, Tracey L. ; Garrett, Nigel J. ; Samsunder, Natasha ; Abdool Karim, Quarraisha ; Abdool Karim, Salim S. ; Riou, Catherine ; Burgers, Wendy A. ;
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    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 − CD38 high ) 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.


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