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

Keiko Fujisaki, Shogo Okazaki, Shuhei Ogawa, Miyama Takeda, Eiji Sugihara, Kenichi Imai, Seiya Mizuno, Satoru Takahashi, Ryo Goitsuka

研究成果: ジャーナルへの寄稿学術論文査読

抄録

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. The Journal of Immunology, 2024, 213: 296–305.

本文言語英語
ページ(範囲)296-305
ページ数10
ジャーナルJournal of Immunology
213
3
DOI
出版ステータス出版済み - 01-08-2024

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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