Restricted Clonality and Limited Germinal Center Reentry Characterize Memory B Cell Reactivation by Boosting
Restricted Clonality and Limited Germinal Center Reentry Characterize Memory B Cell Reactivation by Boosting
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DOI：
10.1016/j.cell.2019.11.032
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发表时间：
2020-01-09
期刊：
影响因子：
64.5
通讯作者：
Victora, Gabriel D.
中科院分区：
文献类型：
--
作者：
Mesin, Luka;Schiepers, Arien;Victora, Gabriel D.
反复暴露于病原体或其抗原触发回忆性抗体应答，其在幅度和亲和力上高于初次应答。这些涉及记忆B细胞（MBC）克隆的重新接合，其多样性和特异性决定了随后抗体反应的广度和有效性。在小鼠中使用引发-加强模型，我们发现次级应答的特征在于克隆性瓶颈，其限制了引发产生的MBC克隆的大多样性的参与。突变的MBC的再分化在次级生殖中心（GC）内是罕见的，其主要由B细胞组成，而没有先前的GC经验或可检测的克隆扩增。少数MBC克隆，通常来源于较高亲和力的生殖系前体，占大多数的二抗应答，而大多数初级来源的克隆多样性不能通过加强检测到。了解如何应对这一瓶颈可能会提高我们通过疫苗接种引发针对非免疫显性表位的抗体的能力。
Repeated exposure to pathogens or their antigens triggers anamnestic antibody responses that are higher in magnitude and affinity than the primary response. These involve reengagement of memory B cell (MBC) clones, the diversity and specificity of which determine the breadth and effectiveness of the ensuing antibody response. Using prime-boost models in mice, we find that secondary responses are characterized by a clonality bottleneck that restricts the engagement of the large diversity of MBC clones generated by priming. Rediversification of mutated MBCs is infrequent within secondary germinal centers (GCs), which instead consist predominantly of B cells without prior GC experience or detectable clonal expansion. Few MBC clones, generally derived from higher-affinity germline precursors, account for the majority of secondary antibody responses, while most primary-derived clonal diversity is not reengaged detectably by boosting. Understanding how to counter this bottleneck may improve our ability to elicit antibodies to non-immunodominant epitopes by vaccination.