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Single Cell RNA Sequencing of Human Liver Infiltrating B Cells in Primary Biliary Cholangitis (PBC)
- Source :
- The Journal of Immunology. 204:218.23-218.23
- Publication Year :
- 2020
- Publisher :
- The American Association of Immunologists, 2020.
-
Abstract
- Increasing evidence supports the concept that dysregulated B cell differentiation and activation are pivotal in the initiation and progression of autoimmune disorders, in both antibody (Ab)-dependent and Ab-independent mechanisms. Antimitochondrial antibodies (AMA), the serologic hallmark of PBC, are present in greater than 95% of patients with PBC, with a long latency period between the detection of autoantibodies and the onset of clinical disease. However, the mechanisms involved in the role of B cells in the pathogenesis of PBC have remained enigmatic. Herein, we have applied scRNA sequencing to simultaneously characterize B cell repertoire and transcriptome status in blood-liver paired samples from patients with PBC. Our data reveal that there is a dramatic increase in the heterogeneity of the blood CD27− B-cell population in PBC as compared to control. Strikingly, this overwhelmingly expanded naïve-like population were IgM+/IgD+, and encoded by germline sequences. In contrast with blood B cells, the dominant liver CD27− B-cell population is comprised of a high frequency of class-switched clonal B cells, which strongly express MHC class II genes. Upon stimulation with CpG (a surrogate TI-antigen), PBC CD27− B-cell populations markedly expanded and were accompanied by a significantly reduced expression of MARCKS, a newly identified molecule that suppresses active BCR signaling, as compared to healthy controls. Our data indicate that PBC CD27− B-cells exhibit abnormalities and heterogeneity, which may arise from a consistent exposure to TI-antigens. Our findings underscore the significance of B cells in PBC and suggest that more efforts should be placed on PBC B cell immunobiology and as potential therapeutic targets.
- Subjects :
- Immunology
Immunology and Allergy
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 204
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi...........b55258a96f81fe1781984e08267969b5