Single-cell genomics identifies distinct B1 cell developmental pathways and reveals aging-related changes in the B-cell receptor repertoire.
Single-cell genomics identifies distinct B1 cell developmental pathways and reveals aging-related changes in the B-cell receptor repertoire.
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单细胞基因组学识别不同的 B1 细胞发育途径并揭示 B 细胞受体库中与衰老相关的变化
DOI：
10.1186/s13578-022-00795-6
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发表时间：
2022-05-07
影响因子：
7.5
通讯作者：
Yu, Yong
中科院分区：
文献类型：
--
作者：
Luo, Yao;Wang, Jing;Li, Kairui;Li, Mingxia;Xu, Shasha;Liu, Xingjie;Zhang, Zhiwei;Xu, Xiang;Zhang, Yu;Pan, Jiawei;Liu, Pengtao;Gao, Shaorong;Miao, Zhichao;Yu, Yong
B1细胞是自我更新的先天性B淋巴细胞，提供了抵御病原体的第一道防线。B1细胞主要存在于腹膜腔中，并且已知起源于各种胎儿组织，但它们的发育途径和整个成年期B1细胞维持的潜在机制仍不清楚。我们对新生儿、年轻成年人和老年小鼠的腹膜B细胞的转录组和B细胞受体库进行了高通量单细胞分析。对31,718个腹膜B细胞的基因表达分析表明，新生儿腹膜腔含有许多B1祖细胞，新生儿B细胞特异性聚集揭示了腹膜B1细胞发育的两种轨迹，包括前BCR依赖性和前BCR非依赖性途径。我们还在B1细胞转录组中检测到了与年龄相关的显著变化：在不同年龄的B1细胞中，衰老遗传程序的明显差异是显而易见的，我们发现了一个例子，即仅存在于最老小鼠中的B1亚群以脂肪酸受体CD 36的表达为标志。我们还对来自三个年龄组的15，967个腹膜B细胞进行了抗体基因测序，发现B1细胞老化与克隆扩增相关，并且在老年小鼠中扩增的两个B1细胞克隆具有与来自动脉粥样硬化小鼠模型的最近研究的致病连锁细胞类型相同的CDR-H3序列（AGDYDGYWYFDV）。我们的研究不仅为探索B细胞的细胞间差异提供了前所未有的数据资源，而且揭示了新生儿腹腔中存在B1前体细胞亚群，并解剖了前体细胞的发育途径。此外，本研究还发现了老年小鼠B1细胞上CD 36的表达。单细胞B细胞受体测序显示B1细胞衰老与克隆扩增有关。在线版本包含补充材料，可通过10.1186/s13578-022-00795-6获得。
B1 cells are self-renewing innate-like B lymphocytes that provide the first line of defense against pathogens. B1 cells primarily reside in the peritoneal cavity and are known to originate from various fetal tissues, yet their developmental pathways and the mechanisms underlying maintenance of B1 cells throughout adulthood remain unclear. We performed high-throughput single-cell analysis of the transcriptomes and B-cell receptor repertoires of peritoneal B cells of neonates, young adults, and elderly mice. Gene expression analysis of 31,718 peritoneal B cells showed that the neonate peritoneal cavity contained many B1 progenitors, and neonate B cell specific clustering revealed two trajectories of peritoneal B1 cell development, including pre-BCR dependent and pre-BCR independent pathways. We also detected profound age-related changes in B1 cell transcriptomes: clear difference in senescence genetic program was evident in differentially aged B1 cells, and we found an example that a B1 subset only present in the oldest mice was marked by expression of the fatty-acid receptor CD36. We also performed antibody gene sequencing of 15,967 peritoneal B cells from the three age groups and discovered that B1 cell aging was associated with clonal expansion and two B1 cell clones expanded in the aged mice had the same CDR-H3 sequence (AGDYDGYWYFDV) as a pathogenically linked cell type from a recent study of an atherosclerosis mouse model. Beyond offering an unprecedent data resource to explore the cell-to-cell variation in B cells, our study has revealed that B1 precursor subsets are present in the neonate peritoneal cavity and dissected the developmental pathway of the precursor cells. Besides, this study has found the expression of CD36 on the B1 cells in the aged mice. And the single-cell B-cell receptor sequencing reveals B1 cell aging is associated with clonal expansion. The online version contains supplementary material available at 10.1186/s13578-022-00795-6.
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影响因子：
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作者：
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