B Cells of Early-life Origin Defined by RAG2-based Lymphoid Cell Tracking under Native Hematopoietic Conditions.

IF 3.6 3区 医学 Q2 IMMUNOLOGY
Keiko Fujisaki, Shogo Okazaki, Shuhei Ogawa, Miyama Takeda, Eiji Sugihara, Kenichi Imai, Seiya Mizuno, Satoru Takahashi, Ryo Goitsuka
{"title":"B Cells of Early-life Origin Defined by RAG2-based Lymphoid Cell Tracking under Native Hematopoietic Conditions.","authors":"Keiko Fujisaki, Shogo Okazaki, Shuhei Ogawa, Miyama Takeda, Eiji Sugihara, Kenichi Imai, Seiya Mizuno, Satoru Takahashi, Ryo Goitsuka","doi":"10.4049/jimmunol.2400072","DOIUrl":null,"url":null,"abstract":"<p><p>During the perinatal period, the immune system sets the threshold to select either response or tolerance to environmental Ags, which leads to the potential to provide a lifetime of protection and health. B-1a B cells have been demonstrated to develop during this perinatal time window, showing a unique and restricted BCR repertoire, and these cells play a major role in natural Ab secretion and immune regulation. In the current study, we developed a highly efficient temporally controllable RAG2-based lymphoid lineage cell labeling and tracking system and applied this system to understand the biological properties and contribution of B-1a cells generated at distinct developmental periods to the adult B-1a compartments. This approach revealed that B-1a cells with a history of RAG2 expression during the embryonic and neonatal periods dominate the adult B-1a compartment, including those in the bone marrow (BM), peritoneal cavity, and spleen. Moreover, the BCR repertoire of B-1a cells with a history of RAG2 expression during the embryonic period was restricted, becoming gradually more diverse during the neonatal period, and then heterogeneous at the adult stage. Furthermore, more than half of plasmablasts/plasma cells in the adult BM had embryonic and neonatal RAG2 expression histories. Moreover, BCR analysis revealed a high relatedness between BM plasmablasts/plasma cells and B-1a cells derived from embryonic and neonatal periods, suggesting that these cell types have a common origin. Taken together, these findings define, under native hematopoietic conditions, the importance in adulthood of B-1a cells generated during the perinatal period.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4049/jimmunol.2400072","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

During the perinatal period, the immune system sets the threshold to select either response or tolerance to environmental Ags, which leads to the potential to provide a lifetime of protection and health. B-1a B cells have been demonstrated to develop during this perinatal time window, showing a unique and restricted BCR repertoire, and these cells play a major role in natural Ab secretion and immune regulation. In the current study, we developed a highly efficient temporally controllable RAG2-based lymphoid lineage cell labeling and tracking system and applied this system to understand the biological properties and contribution of B-1a cells generated at distinct developmental periods to the adult B-1a compartments. This approach revealed that B-1a cells with a history of RAG2 expression during the embryonic and neonatal periods dominate the adult B-1a compartment, including those in the bone marrow (BM), peritoneal cavity, and spleen. Moreover, the BCR repertoire of B-1a cells with a history of RAG2 expression during the embryonic period was restricted, becoming gradually more diverse during the neonatal period, and then heterogeneous at the adult stage. Furthermore, more than half of plasmablasts/plasma cells in the adult BM had embryonic and neonatal RAG2 expression histories. Moreover, BCR analysis revealed a high relatedness between BM plasmablasts/plasma cells and B-1a cells derived from embryonic and neonatal periods, suggesting that these cell types have a common origin. Taken together, these findings define, under native hematopoietic conditions, the importance in adulthood of B-1a cells generated during the perinatal period.

在原生造血条件下通过基于 RAG2 的淋巴细胞追踪确定生命早期起源的 B 细胞
在围产期,免疫系统设定了阈值,以选择对环境抗体的反应或耐受,从而有可能提供终生的保护和健康。事实证明,B-1a B 细胞在围产期的这个时间窗口中发育,显示出独特而受限的 BCR 复合物,这些细胞在天然抗体分泌和免疫调节中发挥着重要作用。在目前的研究中,我们开发了一种基于 RAG2 的高效时间可控淋巴系细胞标记和追踪系统,并应用该系统了解了在不同发育时期产生的 B-1a 细胞的生物学特性及其对成年 B-1a 区系的贡献。这种方法揭示了胚胎期和新生儿期RAG2表达历史的B-1a细胞在成人B-1a区系中占主导地位,包括骨髓(BM)、腹腔和脾脏中的B-1a细胞。此外,在胚胎期有 RAG2 表达史的 B-1a 细胞的 BCR 重排是受限的,在新生儿期逐渐变得多样化,然后在成年阶段变得异质。此外,成人骨髓中一半以上的浆细胞/浆细胞具有胚胎期和新生儿期的 RAG2 表达历史。此外,BCR 分析表明,来自胚胎期和新生儿期的 BM 浆细胞/浆细胞与 B-1a 细胞之间有很高的亲缘关系,这表明这些细胞类型有共同的起源。综上所述,这些研究结果表明,在原生造血条件下,围产期产生的 B-1a 细胞对成年期的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of immunology
Journal of immunology 医学-免疫学
CiteScore
8.20
自引率
2.30%
发文量
495
审稿时长
1 months
期刊介绍: The JI publishes novel, peer-reviewed findings in all areas of experimental immunology, including innate and adaptive immunity, inflammation, host defense, clinical immunology, autoimmunity and more. Special sections include Cutting Edge articles, Brief Reviews and Pillars of Immunology. The JI is published by The American Association of Immunologists (AAI)
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信