美国斯克里普斯研究所Shane Crotty课题组在研究中取得进展。他们研究出在非常罕见的前体B细胞条件下的多种启动结果。这一研究成果发表在2025年3月31日出版的国际学术期刊《免疫学》上。

研究组揭示了生殖系靶向疫苗递送和佐剂选择如何影响非人类灵长类动物中异常罕见的BG18样HIV广泛中和抗体前体B细胞的启动（5千万分之一）。与其他条件相比，只有以皂苷佐剂SMNP为主题的递增剂量（ED）启动免疫才能在生发中心（GCs）诱导可检测的BG18样细胞。各组均有较强的GC反应，但在50%的动物中只有ED+SMNP和推注+SMNP诱导了BG18样记忆B细胞。一组具有与ED+SMNP相当的疫苗特异性GC反应，但缺乏BG18样B细胞。与ED+SMNP相比，激活组存在BG18样记忆B细胞，但体细胞超突变和亲和性较低。这一结果与引物后抗体滴度呈负相关，表明抗体反馈显著影响罕见的前体B细胞反应。因此，抗原和炎症刺激广泛影响稀有B细胞的启动和亲和成熟。

据介绍，罕见的幼稚B细胞具有特殊的病原体识别特征，能够对保护性免疫做出巨大贡献，但很少参与免疫反应。

附：英文原文

Title: Diverse priming outcomes under conditions of very rare precursor B cells

Author: Patrick J. Madden, Ester Marina-Zárate, Kristen A. Rodrigues, Jon M. Steichen, Monolina Shil, Kaiyuan Ni, Katarzyna Kaczmarek Michaels, Laura Maiorino, Amit A. Upadhyay, Swati Saha, Arpan Pradhan, Oleksandr Kalyuzhiny, Alessia Liguori, Paul G. Lopez, Ivy Phung, Claudia Flynn, Amelia Zhou, Mariane B. Melo, Ashley Lemnios, Nicole Phelps, Erik Georgeson, Nushin Alavi, Michael Kubitz, Danny Lu, Saman Eskandarzadeh, Amanda Metz, Oscar L. Rodriguez, Kaitlyn Shields, Steven Schultze, Melissa L. Smith, Brandon S. Healy, Deuk Lim, Vanessa R. Lewis, Elana Ben-Akiva, William Pinney, Justin Gregory, Shuhao Xiao, Diane G. Carnathan, Sudhir Pai Kasturi, Corey T. Watson, Steven E. Bosinger, Guido Silvestri, William R. Schief, Darrell J. Irvine, Shane Crotty

Issue&Volume: 2025-03-31

Abstract: Rare naive B cells have special pathogen-recognition features that enable outsized contributions to protective immunity but infrequently participate in immune responses. We investigatee how germline-targeting vaccine delivery and adjuvant selection affect priming of exceptionally rare BG18-like HIV broadly neutralizing antibody-precursor B cells (<1-in-50 million) in non-human primates. Only escalating dose (ED) priming immunization using the saponin adjuvant SMNP elicited detectable BG18-like cells in germinal centers (GCs) compared with other conditions. All groups had strong GC responses, but only ED+SMNP and bolus+SMNP induced BG18-like memory B cells in >50% of animals. One group had vaccine-specific GC responses equivalent to ED+SMNP but scarce BG18-like B cells. Following homologous boosting, BG18-like memory B cells were present in a bolus priming group but with lower somatic hypermutation and affinities than ED+SMNP. This outcome inversely associated with post-prime antibody titers, suggesting antibody feedback significantly influences rare precursor B cell responses. Thus, antigen and inflammatory stimuli extensively impact priming and affinity maturation of rare B cells.

DOI: 10.1016/j.immuni.2025.03.003

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00121-9