Max Planck Research Group Molecular Immunology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
J Exp Med. 2013 Feb 11;210(2):389-99. doi: 10.1084/jem.20121970. Epub 2013 Jan 14.
Antibodies can protect from Plasmodium falciparum (Pf) infection and clinical malaria disease. However, in the absence of constant reexposure, serum immunoglobulin (Ig) levels rapidly decline and full protection from clinical symptoms is lost, suggesting that B cell memory is functionally impaired. We show at the single cell level that natural Pf infection induces the development of classical memory B cells (CM) and atypical memory B cells (AtM) that produce broadly neutralizing antibodies against blood stage Pf parasites. CM and AtM contribute to anti-Pf serum IgG production, but only AtM show signs of active antibody secretion. AtM and CM were also different in their IgG gene repertoire, suggesting that they develop from different precursors. The findings provide direct evidence that natural Pf infection leads to the development of protective memory B cell antibody responses and suggest that constant immune activation rather than impaired memory function leads to the accumulation of AtM in malaria. Understanding the memory B cell response to natural Pf infection may be key to the development of a malaria vaccine that induces long-lived protection.
抗体可以预防恶性疟原虫（Pf）感染和临床疟疾疾病。然而，在没有持续重新暴露的情况下，血清免疫球蛋白（Ig）水平迅速下降，完全失去对临床症状的保护，这表明 B 细胞记忆功能受损。我们在单细胞水平上表明，天然 Pf 感染诱导产生了产生针对血阶段 Pf 寄生虫的广泛中和抗体的经典记忆 B 细胞（CM）和非典型记忆 B 细胞（AtM）。CM 和 AtM 有助于抗 Pf 血清 IgG 的产生，但只有 AtM 显示出活跃的抗体分泌迹象。AtM 和 CM 在 IgG 基因库方面也存在差异，这表明它们是由不同的前体发展而来的。这些发现提供了直接证据，表明天然 Pf 感染会导致保护性记忆 B 细胞抗体反应的发展，并表明持续的免疫激活而不是记忆功能受损导致 AtM 在疟疾中的积累。了解对天然 Pf 感染的记忆 B 细胞反应可能是开发诱导长期保护的疟疾疫苗的关键。
