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Transcriptome-Based Study of Tim-1- B Cells and Tim-1+ Regulatory B Cells

Q. Fu, K. Lee, C. G. Rickert, G. Huai, K. Deng, N. Feeney, N. Tanimine, A. G. Cuenca, S. Deng, J. F. Markmann

Center for Transplant Science, MGH, Boston, MA

Meeting: 2020 American Transplant Congress

Abstract number: 544

Keywords: B cells

Session Information

Session Name: B-cells / Antibodies /Autoimmunity

Session Type: Oral Abstract Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:45pm

 Presentation Time: 4:03pm-4:15pm

Location: Virtual

*Purpose: Tim-1 signaling has an important role in maintaining the function of Regulatory B cells. Our previous study suggested Tim-1+ Bregs can prolong the survival of islets significantly in an allo-transplantation model (Balb/c to B6). In this study, we analyzed transcriptional data to determine potential pathways of tolerance induction by TIM-1+ Bregs.

*Methods: C57BL/6 mice were given anti-TIM-1, anti-CD45RB, and irradiated BALB/c splenocytes. On day 14, TIM-1+ and TIM-1- B cells were sorted, and RNA was extracted for RNA sequencing. Naïve C57BL/6 B cell RNA was used as a control. The data were analyzed using R (version: 3.6.1).

*Results: In comparison with the transcripts of the naïve B cell group, the Tim-1- B cell group (n=3) contained 139 differentially expressed genes (DEGs, Log2 |FC| > 1 and P < 0.05), among which 68 transcripts were up-regulated and 71 transcripts were down-regulated. In contrast, the Tim-1+ Breg group (n=3) contained 900 DEGs (759 up-regulated and 141 down-regulated). Between the Tim-1- and Tim-1+ B cell groups, there were 972 transcripts up-regulated and 53 transcripts down-regulated in the Tim-1+ group. Pearson correlation analysis (PCA) found the transcripts of Tim-1- B cells and Tim-1+ Bregs to be significantly different (P < 0.05, Fig. A). Ten of the most different DEGs (according to the contributed score) were: CDC6, Pparg, Rxra, Tyms, Slc11a1, Emr1, Clec1b, Tlr8, Ckap2, and C2 (Fig. B). GSEA enrichment analysis displayed up-regulated DEGs as mainly enriched in 28 different pathways (|NES|>1, NOM p-val<0.05, FDR q-val<0.25). Notable pathways include: angiogenesis, IL6-Jak-Stats signaling, IL-2-Stat5 signaling and TGF-beta signaling (Fig. C).

*Conclusions: Significant transcriptional differences were found between naïve B cells, Tim-1-B cells, and Tim-1+ Bregs. These differences indicate potential mechanistic pathways responsible for suppression of immune response and prolongation of graft survival by Tim-1+ Bregs. Further research on these DEGs is ongoing in vitro.

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To cite this abstract in AMA style:

Fu Q, Lee K, Rickert CG, Huai G, Deng K, Feeney N, Tanimine N, Cuenca AG, Deng S, Markmann JF. Transcriptome-Based Study of Tim-1- B Cells and Tim-1+ Regulatory B Cells [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/transcriptome-based-study-of-tim-1-b-cells-and-tim-1-regulatory-b-cells/. Accessed June 6, 2025.

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