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恶性疟原虫特异性 IgM B 细胞在儿童中占主导地位，随着疟疾而扩增，并产生功能性 IgM。

Plasmodium falciparum-specific IgM B cells dominate in children, expand with malaria, and produce functional IgM.

机构信息

Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD.

Molecular and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD.

出版信息

J Exp Med. 2021 Apr 5;218(4). doi: 10.1084/jem.20200901.

DOI:10.1084/jem.20200901
PMID:33661303
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7938365/
Abstract

IgG antibodies play a role in malaria immunity, but whether and how IgM protects from malaria and the biology of Plasmodium falciparum (Pf)-specific IgM B cells is unclear. In a Mali cohort spanning infants to adults, we conducted longitudinal analyses of Pf- and influenza-specific B cells. We found that Pf-specific memory B cells (MBCs) are disproportionally IgM+ and only gradually shift to IgG+ with age, in contrast to influenza-specific MBCs that are predominantly IgG+ from infancy to adulthood. B cell receptor analysis showed Pf-specific IgM MBCs are somatically hypermutated at levels comparable to influenza-specific IgG B cells. During acute malaria, Pf-specific IgM B cells expand and upregulate activation/costimulatory markers. Finally, plasma IgM was comparable to IgG in inhibiting Pf growth and enhancing phagocytosis of Pf by monocytes in vitro. Thus, somatically hypermutated Pf-specific IgM MBCs dominate in children, expand and activate during malaria, and produce IgM that inhibits Pf through neutralization and opsonic phagocytosis.

摘要

IgG 抗体在疟疾免疫中发挥作用，但 IgM 是否以及如何保护免受疟疾感染，以及疟原虫（Pf）特异性 IgM B 细胞的生物学特性尚不清楚。在马里的一个队列中，我们对 Pf 和流感特异性 B 细胞进行了纵向分析。我们发现，Pf 特异性记忆 B 细胞（MBC）不成比例地为 IgM+，并且仅随着年龄的增长逐渐向 IgG+转变，而流感特异性 MBC 则从婴儿期到成年期均主要为 IgG+。B 细胞受体分析表明，Pf 特异性 IgM MBC 的体细胞高频突变水平与流感特异性 IgG B 细胞相当。在急性疟疾期间，Pf 特异性 IgM B 细胞扩增并上调激活/共刺激标志物。最后，体外实验表明，血浆 IgM 与 IgG 一样能够抑制 Pf 的生长并增强单核细胞对 Pf 的吞噬作用。因此，体细胞高频突变的 Pf 特异性 IgM MBC 在儿童中占主导地位，在疟疾期间扩增并激活，并产生 IgM 通过中和和调理吞噬作用抑制 Pf 的生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/d7634fa555fe/JEM_20200901_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/83a759b981d7/JEM_20200901_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/d0be12e8b608/JEM_20200901_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/d35249e6447d/JEM_20200901_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/f42f5b05476d/JEM_20200901_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/afb555b384a6/JEM_20200901_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/cf1bd2e3a7e6/JEM_20200901_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/3c3eba3c621d/JEM_20200901_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/396b544e101a/JEM_20200901_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/9c28f8d09e6c/JEM_20200901_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/d7634fa555fe/JEM_20200901_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/83a759b981d7/JEM_20200901_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/d0be12e8b608/JEM_20200901_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/d35249e6447d/JEM_20200901_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/f42f5b05476d/JEM_20200901_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/afb555b384a6/JEM_20200901_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/cf1bd2e3a7e6/JEM_20200901_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/3c3eba3c621d/JEM_20200901_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/396b544e101a/JEM_20200901_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/9c28f8d09e6c/JEM_20200901_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1985/7938365/d7634fa555fe/JEM_20200901_FigS5.jpg

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IgM in human immunity to malaria.

Sci Adv. 2019-9-25

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