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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