Sacha C R, Vandergrift N, Jeffries T L, McGuire E, Fouda G G, Liebl B, Marshall D J, Gurley T C, Stiegel L, Whitesides J F, Friedman J, Badiabo A, Foulger A, Yates N L, Tomaras G D, Kepler T B, Liao H X, Haynes B F, Moody M A, Permar S R
Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Department of Microbiology and Department of Mathematics & Statistics, Boston University School of Medicine, Boston, Massachusetts, USA.
Mucosal Immunol. 2015 Mar;8(2):316-26. doi: 10.1038/mi.2014.69. Epub 2014 Aug 6.
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.
一种成功的HIV-1疫苗必须引发能够阻止黏膜病毒传播的免疫反应，尽管具有保护性的HIV-1包膜（Env）特异性黏膜抗体的功能作用仍不清楚。初乳是易于获取的黏膜B细胞的丰富来源，这可能有助于确定有助于预防产后HIV-1传播的黏膜抗体反应。为了研究HIV-1 Env特异性初乳B细胞库，从17名慢性HIV感染的哺乳期妇女中分离出单个B细胞，产生了51种血液和39种初乳HIV-1 Env特异性B细胞抗体。所有源自初乳的HIV-1 Env特异性抗体均为免疫球蛋白（Ig）G1同种型，其重链互补决定区3（CDR3）的平均长度和突变频率与从血液中分离出的相似。然而，初乳中可变重链（VH）基因亚家族1(∼)69的使用率高于血液中的HIV-1 Env反应性抗体（49%对20%，P=0.006，Fisher精确检验）。此外，与从血液中分离出的抗体相比，更多的HIV-1 Env特异性初乳抗体是gp120特异性的（44%对16%，P=0.005，Fisher精确检验）。鉴定出一个跨区室的HIV-1 Env特异性克隆B细胞谱系。初乳B细胞抗体的这些独特特征表明HIV-1特异性IgG1分泌记忆B细胞选择性归巢至乳腺，并且对通过疫苗接种靶向黏膜B细胞群体具有启示意义。
