Restricted isotype, distinct variable gene usage, and high rate of gp120-specificity of HIV-1 Envelope-specific B cells in colostrum compared to those in blood of HIV-1-infected, lactating African women

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 Envspecific 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. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Corresponding author. Mailing address: Human Vaccine Institute, Duke University Medical Center, Box 103020, Durham, NC 27710. Fax: 919-684-5230. Phone: 919-684-2515. [email protected]. *These authors contributed equally to the work. The authors have no conflicts of interest. Disclosure We have no conflicts of interest to disclose. HHS Public Access Author manuscript Mucosal Immunol. Author manuscript; available in PMC 2015 September 01. Published in final edited form as: Mucosal Immunol. 2015 March ; 8(2): 316–326. doi:10.1038/mi.2014.69. A uhor M anscript