Affinity maturation selects B cells expressing somatically mutated antibody variants with improved antigen-binding properties to protect from invading pathogens. We determined the molecular mechanism underlying the clonal selection and affinity maturation of human B cells expressing protective antibodies against the circumsporozoite protein of the malaria parasite Plasmodium falciparum (PfCSP). We show in molecular detail that the repetitive nature of PfCSP facilitates direct homotypic interactions between two PfCSP repeat-bound monoclonal antibodies, thereby improving antigen affinity and B cell activation. These data provide a mechanistic explanation for the strong selection of somatic mutations that mediate homotypic antibody interactions after repeated parasite exposure in humans. Our findings demonstrate a different mode of antigen-mediated affinity maturation to improve antibody responses to PfCSP and presumably other repetitive antigens.

中文翻译：

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反同型亲和力成熟可改善人类 B 细胞针对重复表位的反应。


亲和力成熟会选择表达体细胞突变抗体变体的 B 细胞，这些抗体变体具有改进的抗原结合特性，以防止病原体入侵。我们确定了人类 B 细胞克隆选择和亲和力成熟的分子机制，该细胞表达针对疟原虫恶性疟原虫(PfCSP) 的环子孢子蛋白的保护性抗体。我们以分子细节证明，PfCSP 的重复性质促进两个 PfCSP 重复结合的单克隆抗体之间的直接同型相互作用，从而提高抗原亲和力和 B 细胞活化。这些数据为人类反复接触寄生虫后介导同型抗体相互作用的体细胞突变的强烈选择提供了机制解释。我们的研究结果证明了抗原介导的亲和力成熟的不同模式，可以改善抗体对 PfCSP 和可能的其他重复抗原的反应。