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PLoS One. 2013 Dec 16;8(12):e84185. doi: 10.1371/journal.pone.0084185. eCollection 2013.

B cell responses to HIV antigen are a potent correlate of viremia in HIV-1 infection and improve with PD-1 blockade.

Author information

1
Department of Pathology, Microbiology and Immunology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
2
Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
3
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
4
Department of Pathology, Microbiology and Immunology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America ; Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.

Abstract

Infection with Human Immunodeficiency Virus Type 1 (HIV-1) induces defects of both cellular and humoral immune responses. Impaired CD4+ T cell help and B cell dysfunction may partially explain the low frequency of broadly neutralizing antibodies in HIV-infected individuals. To understand the extent of B cell dysfunction during HIV infection, we assessed the level of B cell activation at baseline and after stimulation with a variety of antigens. Increased levels of viremia were associated with higher baseline expression of the activation marker CD86 on B cells and with decreased ability of B cells to increase expression of CD86 after in vitro stimulation with inactivated HIV-1. In a series of cell isolation experiments B cell responses to antigen were enhanced in the presence of autologous CD4+ T cells. HIV infected individuals had a higher frequency of PD-1 expression on B cells compared to HIV- subjects and PD-1 blockade improved B cell responsiveness to HIV antigen, suggesting that inhibitory molecule expression during HIV-1 infection may contribute to some of the observed B cell defects. Our findings demonstrate that during chronic HIV infection, B cells are activated and lose full capacity to respond to antigen, but suppression of inhibitory pressures as well as a robust CD4+ T cell response may help preserve B cell function.

PMID:
24358343
PMCID:
PMC3865293
DOI:
10.1371/journal.pone.0084185
[Indexed for MEDLINE]
Free PMC Article

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