title: Phenotypes and distribution of mucosal memory B-cell populations in the SIV/SHIV rhesus macaque model.
abstract: As vaccine-elicited antibodies have now been associated with HIV protective efficacy, a thorough understanding of mucosal and systemic B-cell development and maturation is needed. We phenotyped mucosal memory B-cells, investigated isotype expression and homing patterns, and defined plasmablasts and plasma cells at three mucosal sites (duodenum, jejunum and rectum) in rhesus macaques, the commonly used animal model for pre-clinical vaccine studies. Unlike humans, macaque mucosal memory B-cells lacked CD27 expression; only two sub-populations were present: naïve (CD21(+)CD27(-)) and tissue-like (CD21(-)CD27(-)) memory. Similar to humans, IgA was the dominant isotype expressed. The homing markers CXCR4, CCR6, CCR9 and α4β7 were differentially expressed between naïve and tissue-like memory B-cells. Mucosal plasmablasts were identified as CD19(+)CD20(+/-)HLA-DR(+)Ki-67(+)IRF4(+)CD138(+/-) and mucosal plasma cells as CD19(+)CD20(-)HLA-DR(-)Ki-67(-)IRF4(+)CD138(+). Both populations were CD39(+/-)CD27(-). Plasma cell phenotype was confirmed by spontaneous IgA secretion by ELISpot of positively-selected cells and J-chain expression by real-time PCR. Duodenal, jejunal and rectal samples were similar in B-cell memory phenotype, isotype expression, homing receptors and plasmablast/plasma cell distribution among the three tissues. Thus rectal biopsies adequately monitor B-cell dynamics in the gut mucosa, and provide a critical view of mucosal B-cell events associated with development of vaccine-elicited protective immune responses and SIV/SHIV pathogenesis and disease control.
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, USA.
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, USA.
authors.forename: Venkatramanan
authors.initials: V
authors.lastname: Mohanram
authors.affiliation: Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD 20892, USA.
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, USA. Electronic address: guroffm@mail.nih.gov.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D004195:Disease Models, Animal; D004386:Duodenum / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D050835:Interferon Regulatory Factors / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D007583:Jejunum / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism; D008253:Macaca mulatta; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D012007:Rectum / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology; D053668:Syndecan-1 / Q000276:immunology / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
chemical_list: D018941:Antigens, CD19; D018951:Antigens, CD20; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D050835:Interferon Regulatory Factors; D019394:Ki-67 Antigen; D019707:Receptors, Chemokine; D053668:Syndecan-1; D000099218:Interferon Regulatory Factor-4
keywords: Homing markers; Mucosal memory B cell phenotypes and distribution; Plasmablasts/plasma cells; SIV/SHIV rhesus macaque model