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

Mucosal Immunol. 2015 Mar;8(2):316-26. doi: 10.1038/mi.2014.69. Epub 2014 Aug 6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans
  • Antibody Formation / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • CD4 Lymphocyte Count
  • Clonal Evolution
  • Colostrum / cytology
  • Colostrum / immunology*
  • Complementarity Determining Regions / genetics
  • Epitopes, B-Lymphocyte / immunology
  • Female
  • HIV Antibodies / immunology
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp41 / immunology
  • HIV Infections / blood
  • HIV Infections / genetics*
  • HIV Infections / immunology*
  • HIV Infections / transmission
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • Immunologic Memory
  • Immunophenotyping
  • Infectious Disease Transmission, Vertical
  • Lactation*
  • Mutation Rate
  • Phenotype
  • Somatic Hypermutation, Immunoglobulin
  • Viral Load

Substances

  • Complementarity Determining Regions
  • Epitopes, B-Lymphocyte
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region