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

• Published in: PloS one 2013-12, Vol.8 (12), p.e84185
• Main Authors: Nicholas, Katherine J, Zern, Emily K, Barnett, Louise, Smith, Rita M, Lorey, Shelly L, Copeland, Courtney A, Sadagopal, Shanmugalakshmi, Kalams, Spyros A
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Antibodies; Antigens; B cells; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B7-2 Antigen - metabolism; CD4 antigen; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD86 antigen; Cell activation; Chronic infection; Defects; Disease susceptibility; Health aspects; HIV; HIV Antigens - immunology; HIV infections; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immune response (humoral); Interleukin-2 Receptor alpha Subunit - metabolism; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes B; Lymphocytes T; PD-1 protein; Physicians; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Stimulation; T cell receptors; T cells; Viral infections; Viral Load; Viremia; Viremia - immunology; Viremia - metabolism; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084185

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.