title: B cell responses to HIV antigen are a potent correlate of viremia in HIV-1 infection and improve with PD-1 blockade.
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.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Nicholas
authors.affiliation: Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Zern
authors.affiliation: Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Louise
authors.initials: L
authors.lastname: Barnett
authors.affiliation: Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Rita M
authors.initials: RM
authors.lastname: Smith
authors.affiliation: Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Lorey
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Copeland
authors.affiliation: Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Shanmugalakshmi
authors.initials: S
authors.lastname: Sadagopal
authors.affiliation: 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.
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000276:immunology* / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; D015488:HIV Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D061026:Programmed Cell Death 1 Receptor