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 IgG1 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% versus 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% versus 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.