Thomas Peter, Rees-Spear Chloe, Griffith Sarah, Muir Luke, Touizer Emma, Andrabi Raiees, Priest Richard, Percival-Alwyn Jennifer, Hayward Darryl, Buxton Amanda, Traylen William, Chain Benny, Wattam Trevor, Nandin Irene Sanjuan, McCoy Laura E
Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
Biopharmaceutical Molecular Discovery Group, GSK, Gunnels Wood Rd, Stevenage SG1 2NY, UK.
iScience. 2024 Mar 11;27(4):109495. doi: 10.1016/j.isci.2024.109495. eCollection 2024 Apr 19.
Antigen-specific antibody infusion is known to enhance or suppress germinal center (GC) responses depending on the affinity of the infusion. We hypothesized that infusing monoclonal antibodies (mAbs) of escalating affinity during an immunization regimen may progressively escalate selection pressure on competing B cells, increasing their affinity. To test this, we immunized mice with HIV envelope gp120 and infused CD4 binding-site (CD4bs)-specific mAbs. While mAb infusion reduced somatic hypermutation (SHM) and affinity in most CD4bs-specific B cells, a sub-population was identified with greater SHM and affinity than control. High-throughput sequencing of plasma cells revealed that CD4bs-specific plasma cells possessed elevated SHM after mAb infusion, with phylogenetic tree topology that suggested more rapid differentiation. We therefore conclude, in accordance with other studies, that high-affinity mAb infusion primarily suppresses recruitment of most competing B cells but can increase and expedite affinity maturation of certain epitope-specific B cells.
已知抗原特异性抗体输注会根据输注抗体的亲和力增强或抑制生发中心（GC）反应。我们推测，在免疫方案中输注亲和力不断升高的单克隆抗体（mAb）可能会逐渐增加对竞争B细胞的选择压力，从而提高其亲和力。为了验证这一点，我们用HIV包膜糖蛋白gp120免疫小鼠，并输注CD4结合位点（CD4bs）特异性mAb。虽然mAb输注降低了大多数CD4bs特异性B细胞的体细胞超突变（SHM）和亲和力，但我们鉴定出了一个亚群，其SHM和亲和力高于对照组。对浆细胞进行高通量测序发现，mAb输注后，CD4bs特异性浆细胞的SHM升高，系统发育树拓扑结构表明其分化更快。因此，与其他研究一致，我们得出结论，高亲和力mAb输注主要抑制大多数竞争B细胞的募集，但可以增加并加速某些表位特异性B细胞的亲和力成熟。
