title: Loss of marginal zone B-cells in SHIVSF162P4 challenged rhesus macaques despite control of viremia to low or undetectable levels in chronic infection.
abstract: Marginal zone (MZ) B cells generate T-independent antibody responses to pathogens before T-dependent antibodies arise in germinal centers. They have been identified in cynomolgus monkeys and monitored during acute SIV infection, yet have not been well-studied in rhesus macaques. Here we characterized rhesus macaque MZ B cells, present in secondary lymphoid tissue but not peripheral blood, as CD19(+), CD20(+), CD21(hi), IgM(+), CD22(+), CD38(+), BTLA(+), CD40(+), CCR6(+) and BCL-2(+). Compared to healthy macaques, SHIVSF162P4-infected animals showed decreased total B cells and MZ B cells and increased MZ B cell Ki-67 expression early in chronic infection. These changes persisted in late chronic infection, despite viremia reductions to low or undetectable levels. Expression levels of additional phenotypic markers and RNA PCR array analyses were in concert with continued low-level activation and diminished function of MZ B cells. We conclude that MZ B-cell dysregulation and dysfunction associated with SIV/HIV infection are not readily reversible.
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, United States.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Demberg
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, United States.
authors.forename: Venkatramanan
authors.initials: V
authors.lastname: Mohanram
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Musich
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, United States.
authors.forename: Egidio
authors.initials: E
authors.lastname: Brocca-Cofano
authors.affiliation: FACS Core, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, United States.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: McKinnon
authors.affiliation: Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD 20892, United States.
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, United States. Electronic address: guroffm@mail.nih.gov.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000737:chemistry / Q000145:classification / Q000276:immunology*; D002908:Chronic Disease; D020869:Gene Expression Profiling; D007075:Immunoglobulin M / Q000032:analysis; D016130:Immunophenotyping; D019394:Ki-67 Antigen / Q000032:analysis; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000473:pathology; D008253:Macaca mulatta; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014766:Viremia
chemical_list: D015703:Antigens, CD; D007075:Immunoglobulin M; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: B cell dysregulation; Marginal zone B cells; Rhesus macaque; Simian–human immunodeficiency virus infection