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CD8-Expressing Transitional B Cells Dominate B Cell Reconstitution in Transplanted Monkeys Receiving Mixed Chimerism Conditioning

K. Pruner, J. Paster, S. Wiebke, O. Jane, H. Isabel, D. Abbas, B. Gilles, M. Joren.

Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA.

Meeting: 2018 American Transplant Congress

Abstract number: D12

Keywords: B cells, Heart/lung transplantation, Mixed chimerism, Primates

Session Information

Date: Tuesday, June 5, 2018

Session Name: Poster Session D: B-cell / Antibody

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall 4EF

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Introduction

Tolerance of heart or lung allografts have been achieved for the first time in nonhuman primates (NHPs) using a mixed chimerism conditioning regimen. However, the mechanisms leading to this state of unresponsiveness remain unclear. Transitional B cells have been recently highlighted for their IL-10-dependent suppressive capabilities and their potential to assist in Treg development and sustainability. Here, we assessed the prevalence of transitional B cells during leukocyte reconstitution in conditioned NHP recipients of combined bone marrow and solid organ allografts.

Methods

Solid organ transplants were performed utilizing a depletive therapy consisting of 3Gy TBI, 7Gy thymic irradiation and anti-thymocyte globulin. Donor bone marrow was infused either simultaneously or 2-4 months following organ transplantation. Transitional B cells were defined as CD3-CD20+CD27-CD8+IgM+CD38hi. The phenotype of reconstituting B cells was followed in ten transplanted monkeys using flow cytometry. Sixteen healthy controls (HC) were stained and seven tolerant (TOL) recipients- defined as rejection-free survival more than 300 days in the absence of immunosuppression- were retrospectively stained with timepoints ranging from days 115 to 514 post-BMT.

Results

B cell reconstitution occurred from day 25-80 post-BMT. During this period, transitional B-Cells made up a significantly increased proportion of both the lymphocyte and B cell compartment in the experimental recipients (n=10) as compared to HC (n=16) (2.5% vs 0.4% in lymphocytes p<0.001; 23.4% vs 2.5% in B cell; p<0.001). In contrast, staining of late TOL timepoints (n=7) revealed no significant differences in comparison to HC (n=16) (1.1% vs 0.4% in lymphocytes p=0.32; 5.5% vs 2.2% in B cell; p=0.17).

Conclusion

The prevalence of transitional B cells during lymphocyte reconstitution following mixed chimerism conditioning suggests that this B cell subset may play an important role in the induction but not maintenance of thoracic organ tolerance, perhaps by promoting Tregs.

CITATION INFORMATION: Pruner K., Paster J., Wiebke S., Jane O., Isabel H., Abbas D., Gilles B., Joren M. CD8-Expressing Transitional B Cells Dominate B Cell Reconstitution in Transplanted Monkeys Receiving Mixed Chimerism Conditioning Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Pruner K, Paster J, Wiebke S, Jane O, Isabel H, Abbas D, Gilles B, Joren M. CD8-Expressing Transitional B Cells Dominate B Cell Reconstitution in Transplanted Monkeys Receiving Mixed Chimerism Conditioning [abstract]. https://atcmeetingabstracts.com/abstract/cd8-expressing-transitional-b-cells-dominate-b-cell-reconstitution-in-transplanted-monkeys-receiving-mixed-chimerism-conditioning/. Accessed April 19, 2021.

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