title: Restricted isotype, distinct variable gene usage, and high rate of gp120 specificity of HIV-1 envelope-specific B cells in colostrum compared with those in blood of HIV-1-infected, lactating African women.
abstract: A successful HIV-1 vaccine must elicit immune responses that impede mucosal virus transmission, though functional roles of protective HIV-1 Envelope (Env)-specific mucosal antibodies remain unclear. Colostrum is a rich source of readily accessible mucosal B cells that may help define the mucosal antibody response contributing to prevention of postnatal HIV-1 transmission. To examine the HIV-1 Env-specific colostrum B-cell repertoire, single B cells were isolated from 17 chronically HIV-infected, lactating women, producing 51 blood and 39 colostrum HIV-1 Env-specific B-cell antibodies. All HIV-1 Env-specific colostrum-derived antibodies were immunoglobulin (Ig)G1 isotype and had mean heavy chain complementarity-determining region 3 (CDR3) lengths and mutation frequencies similar to those isolated from blood. However, variable heavy chain (VH) gene subfamily 1(∼)69 usage was higher among colostrum than blood HIV-1 Env-reactive antibodies (49% vs. 20%, P=0.006, Fisher's exact test). Additionally, more HIV-1 Env-specific colostrum antibodies were gp120 specific than those isolated from blood (44% vs. 16%, P=0.005, Fisher's exact test). One cross-compartment HIV-1 Env-specific clonal B-cell lineage was identified. These unique characteristics of colostrum B-cell antibodies suggest selective homing of HIV-1-specific IgG1-secreting memory B cells to the mammary gland and have implications for targeting mucosal B-cell populations by vaccination.
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Sacha
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: N
authors.initials: N
authors.lastname: Vandergrift
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Jeffries
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: E
authors.initials: E
authors.lastname: McGuire
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: G G
authors.initials: GG
authors.lastname: Fouda
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: B
authors.initials: B
authors.lastname: Liebl
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Marshall
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Gurley
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: L
authors.initials: L
authors.lastname: Stiegel
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Whitesides
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: J
authors.initials: J
authors.lastname: Friedman
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: A
authors.initials: A
authors.lastname: Badiabo
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: A
authors.initials: A
authors.lastname: Foulger
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Yates
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Department of Microbiology and Department of Mathematics & Statistics, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: T B
authors.initials: TB
authors.lastname: Kepler
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: H X
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: B F
authors.initials: BF
authors.lastname: Haynes
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Moody
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Permar
mesh_terms: D001741:Black or African American; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018791:CD4 Lymphocyte Count; D060965:Clonal Evolution; D003126:Colostrum / Q000166:cytology / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D016130:Immunophenotyping; D018445:Infectious Disease Transmission, Vertical; D007774:Lactation; D059645:Mutation Rate; D010641:Phenotype; D027041:Somatic Hypermutation, Immunoglobulin; D019562:Viral Load
chemical_list: D022801:Complementarity Determining Regions; D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region
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