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Characterization of Organ-Specific Regulatory B Cells Using Single-Cell RNA Sequencing.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Sep 14; Vol. 12, pp. 711980. Date of Electronic Publication: 2021 Sep 14 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- Regulatory B cells (Breg) are considered as immunosuppressive cells. Different subsets of Breg cells have been identified both in human beings and in mice. However, there is a lack of unique markers to identify Breg cells, and the heterogeneity of Breg cells in different organs needs to be further illuminated. In this study, we performed high-throughput single-cell RNA sequencing (scRNA-seq) and single-cell B-cell receptor sequencing (scBCR-seq) of B cells from the murine spleen, liver, mesenteric lymph nodes, bone marrow, and peritoneal cavity to better define the phenotype of these cells. Breg cells were identified based on the expression of immunosuppressive genes and IL-10-producing B (B10) cell-related genes, to define B10 and non-B10 subsets in Breg cells based on the score of the B10 gene signatures. Moreover, we characterized 19 common genes significantly expressed in Breg cells, including Fcrl5 , Zbtb20 , Ccdc28b , Cd9 , and Ptpn22 , and further analyzed the transcription factor activity in defined Breg cells. Last, a BCR analysis was used to determine the clonally expanded clusters and the relationship of Breg cells across different organs. We demonstrated that Atf3 may potentially modulate the function of Breg cells as a transcription factor and that seven organ-specific subsets of Breg cells are found. Depending on gene expression and functional modules, non-B10 Breg cells exhibited activated the TGF-β pathway, thus suggesting that non-B10 Breg cells have specific immunosuppressive properties different from conventional B10 cells. In conclusion, our work provides new insights into Breg cells and illustrates their transcriptional profiles and BCR repertoire in different organs under physiological conditions.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Yang, Long, Huang, Luo, Bian, Xu, Wang, Yang, Li, Selmi, Gershwin, Zhao and Lian.)
- Subjects :
- Animals
Antigens, Differentiation, B-Lymphocyte analysis
B-Lymphocytes, Regulatory chemistry
Bone Marrow Cells
Clone Cells
Female
Humans
Immunophenotyping
Lymph Nodes cytology
Mice
Mice, Inbred C57BL
Organ Specificity
Peritoneal Cavity cytology
RNA-Seq
Receptors, Antigen, B-Cell genetics
Spleen cytology
Transcription Factors analysis
B-Lymphocytes, Regulatory classification
Lymphoid Tissue cytology
Single-Cell Analysis methods
Transcriptome
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34594327
- Full Text :
- https://doi.org/10.3389/fimmu.2021.711980