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感染对人体 B 细胞区室和抗体应答的影响。

Impact of Infection on Human B Cell Compartment and Antibody Responses.

机构信息

Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico (A.O.U.P.) Paolo Giaccone, University of Palermo, 90127 Palermo, Italy.

Department of Biomedicine, Neurosciences and Advanced Diagnostic (Bi.N.D.), University of Palermo, 90127 Palermo, Italy.

出版信息

Cells. 2022 Sep 17;11(18):2906. doi: 10.3390/cells11182906.

DOI:10.3390/cells11182906
PMID:36139482
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9497247/
Abstract

Tuberculosis (TB) remains one of the most important health challenges worldwide. Control of the TB epidemic has not yet been achieved because of the lack of an effective vaccine and rapid and sensitive diagnostic approaches, as well as the emergence of drug-resistant forms of . Cellular immunity has a pivotal role against infection, but the role of humoral immunity is still controversial. We analyzed the frequency, absolute counts, and phenotypic and functional subsets of B lymphocytes in the peripheral blood of patients with active TB and subjects with latent infection compared to healthy donors. Moreover, we analyzed serum levels of total Ig and their IgA, IgM, and IgG isotypes and the titers of preexisting antibodies against a pool of common viral pathogens. FlowCT and unsupervised clusterization analysis show that patients with active TB and LTBI subjects have modest non-significant reduction in the numbers of circulating B lymphocytes as compared to healthy donors. Moreover, LTBI subjects had high percentages of atypical B cell population and lower percentages of naive and switched memory B cells. These findings were supported by gene expression and GSEA analysis. Moreover, there were no differences between active TB patients, LTBI subjects and HD, either in serum levels of total Ig isotypes or in preexisting IgG antibody titers, to ten different antigens from eight common pathogenic viruses, clearly demonstrating that either active or latent infection preserves the antibody production capacity of long-lived plasma cells. Thus, our results agree with previous studies reporting unaltered B cell frequencies in the blood of active TB patients and LTBI individuals as compared to healthy controls.

摘要

结核病(TB)仍然是全球最重要的健康挑战之一。由于缺乏有效的疫苗和快速、敏感的诊断方法,以及耐药形式的出现,结核病的流行尚未得到控制。细胞免疫对 感染具有关键作用,但体液免疫的作用仍存在争议。我们分析了活动期结核病患者和潜伏感染患者与健康供体相比外周血 B 淋巴细胞的频率、绝对计数、表型和功能亚群。此外,我们还分析了总 Ig 及其 IgA、IgM 和 IgG 同种型的血清水平以及针对常见病毒病原体池的预先存在抗体的滴度。FlowCT 和无监督聚类分析表明,与健康供体相比,活动性结核病患者和 LTBI 患者的循环 B 淋巴细胞数量略有减少,但无统计学意义。此外,LTBI 患者具有较高比例的非典型 B 细胞群和较低比例的幼稚和转换记忆 B 细胞。这些发现得到了基因表达和 GSEA 分析的支持。此外,活动性结核病患者、LTBI 患者和 HD 之间无论是总 Ig 同种型的血清水平还是针对十种不同抗原的预先存在 IgG 抗体滴度(来自八种常见致病性病毒)均无差异,这清楚地表明无论是活动性还是潜伏性 感染都保留了长寿浆细胞的抗体产生能力。因此,我们的结果与先前的研究一致,即与健康对照组相比,活动性结核病患者和 LTBI 个体的血液中 B 细胞频率没有改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5079/9497247/ac00c8faea92/cells-11-02906-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5079/9497247/90eff7ed1ef5/cells-11-02906-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5079/9497247/845c81638db5/cells-11-02906-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5079/9497247/0c6f1e313dac/cells-11-02906-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5079/9497247/6f097da6b57a/cells-11-02906-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5079/9497247/ac00c8faea92/cells-11-02906-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5079/9497247/90eff7ed1ef5/cells-11-02906-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5079/9497247/e08bf81c15c6/cells-11-02906-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5079/9497247/43d513c0cfb6/cells-11-02906-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5079/9497247/6f097da6b57a/cells-11-02906-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5079/9497247/ac00c8faea92/cells-11-02906-g007.jpg

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