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儿童肺炎支原体感染中BCR重链CDR3库特征的改变

Alterations in BCR heavy chain CDR3 repertoire characteristics in pediatric mycoplasma pneumoniae infection.

作者信息

Chen Yanfei, Yuan Yi, Liu Xingzhu, Li Bin, Meng Lijuan, Xiao Ying, Su Zhongjian, Han Linfei, Li Hong, Deng Lili, Li Jun, Ye Caixia, Zhang Xing

机构信息

Department of Cardiology, Kunming Children's Hospital, Kunming, Yunnan, China.

Department of Immunology, Center of Immunomolecular Engineering, Innovation and Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, China.

出版信息

Front Cell Infect Microbiol. 2025 Jun 12;15:1573511. doi: 10.3389/fcimb.2025.1573511. eCollection 2025.

DOI:10.3389/fcimb.2025.1573511
PMID:40575482
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12198128/
Abstract

INTRODUCTION

Mycoplasma pneumoniae (MP) infection is a leading cause of pediatric pneumonia, triggering a complex immune response in which B cells play a critical role. This study aimed to analyze B cell receptor (BCR) heavy chain CDR3 repertoires in MP patients.

METHODS

Clinical data from 202 children diagnosed with MP were retrospectively analyzed. Flow cytometry was used to assess B cell counts in 99 MP patients and 25 healthy controls (HC). Multiplex PCR was used to construct BCR heavy chain CDR3 repertoires from peripheral blood samples of 8 MP patients and 9 HC.

RESULTS

Serological analysis revealed elevated levels of inflammatory markers, including C-reactive protein, interleukin-6, and ferritin, indicating an active immune response. Flow cytometry showed significantly increased B cell counts in MP patients compared to HC. Immunoglobulin levels were elevated in several patients, indicating immune fluctuations during infection. BCR repertoire analysis revealed increased diversity and altered clonotype distribution in MP patients, with preferential usage of IGHV1-18, IGHV7-4-1, and IGHJ6. MP patients exhibited a bimodal distribution of CDR3 lengths, with significantly longer CDR3 regions. Sixty-eight MP-exclusive clonotypes were identified, with evidence of clonal expansion.

CONCLUSION

These findings suggest that alterations in the BCR heavy chain CDR3 repertoire play a crucial role in the immune response to MP infection and may offer insight into disease progression and therapeutic targets.

摘要

引言

肺炎支原体(MP)感染是小儿肺炎的主要病因,可引发复杂的免疫反应,其中B细胞发挥关键作用。本研究旨在分析MP患者的B细胞受体(BCR)重链互补决定区3(CDR3)库。

方法

回顾性分析202例确诊为MP的儿童的临床资料。采用流式细胞术评估99例MP患者和25例健康对照(HC)的B细胞计数。采用多重聚合酶链反应(PCR)从8例MP患者和9例HC的外周血样本中构建BCR重链CDR3库。

结果

血清学分析显示炎症标志物水平升高,包括C反应蛋白、白细胞介素-6和铁蛋白,表明存在活跃的免疫反应。流式细胞术显示,与HC相比,MP患者的B细胞计数显著增加。部分患者免疫球蛋白水平升高,表明感染期间免疫波动。BCR库分析显示,MP患者的多样性增加,克隆型分布改变,优先使用IGHV1-18、IGHV7-4-1和IGHJ6。MP患者的CDR3长度呈双峰分布,CDR3区域明显更长。鉴定出68种MP特异性克隆型,有克隆扩增的证据。

结论

这些发现表明,BCR重链CDR3库的改变在对MP感染的免疫反应中起关键作用,可能为疾病进展和治疗靶点提供见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c4/12198128/53c223754b20/fcimb-15-1573511-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c4/12198128/b0ff8222aad8/fcimb-15-1573511-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c4/12198128/72df4abb0830/fcimb-15-1573511-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c4/12198128/fbc81e5492d1/fcimb-15-1573511-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c4/12198128/87d7bd8368cb/fcimb-15-1573511-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c4/12198128/53c223754b20/fcimb-15-1573511-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c4/12198128/b0ff8222aad8/fcimb-15-1573511-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c4/12198128/72df4abb0830/fcimb-15-1573511-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c4/12198128/fbc81e5492d1/fcimb-15-1573511-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c4/12198128/87d7bd8368cb/fcimb-15-1573511-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c4/12198128/53c223754b20/fcimb-15-1573511-g005.jpg

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本文引用的文献

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Full-length single-cell BCR sequencing paired with RNA sequencing reveals convergent responses to pneumococcal vaccination.全长单细胞 BCR 测序与 RNA 测序相结合揭示了对肺炎球菌疫苗接种的趋同反应。
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Combining mutation and recombination statistics to infer clonal families in antibody repertoires.
结合突变和重组统计推断抗体库中的克隆家族。
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Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains.多价 DNA 疫苗初免-蛋白疫苗加强免疫诱导的人源 CD4 结合位点抗体中和跨谱系 2 型 HIV 毒株。
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