Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: We have previously reported that transient mixed hematopoietic chimerism induced via donor bone marrow transplantation can achieve tolerance to cardiac allografts in non-human primates (NHPs). The purpose of this study was to measure the frequency and properties of a unique subset of CD8+ B cells, recently identified in our laboratory, in tolerant monkeys.
*Methods: Cynomolgus Macaques underwent organ transplantation followed by injection of donor bone marrow cells with mixed chimerism conditioning consisting of 3Gy TBI, 7Gy thymic irradiation, anti-thymocyte globulin, and a short course of anti-CD154 mAb and CyA therapy. The frequencies of different B cell subsets were measured in the peripheral blood of ten monkeys pre- and post-transplantation. In addition, PBMCs were isolated from peripheral blood of two tolerant animals (recipients of heart plus kidney or heart plus thymus cotransplants) 274 and 847 days post-bone marrow and FACS-sorted into five groups: T cells (CD3+), whole B cells (CD20+), mature B cells (CD20+CD8–CD27+), naïve B cells (CD20+CD8–CD27–), and CD8+ B cells (CD20+CD8+). mRNA was extracted from lysates of each cell population and sequenced using an Illumina NextSeq 500.
*Results: During leukocyte reconstitution following the conditioning procedure, CD8+ B cells exhibited a phenotype reminiscent of transitional B cells (CD20+CD27–IgMhiCD38hi) and the percentage of these cells among peripheral B cells was much higher than that observed in naïve animals (23.4% vs 2.5% respectively; p<0.001). In the two tolerant animals, the CD8+ B cells gene expression suggested an immature profile which included the expression of CD21, CD38, and CD24. Interestingly, however, CD8+ B cells showed an increased expression of the gene encoding for the regulatory protein CD72. In addition, CD8+ B cells had greater expression of CD69 which is involved with TGFbeta production.
*Conclusions: The prevalence of CD8+ B cells expressing genes involved in regulatory immunity after bone marrow transplantation suggests that these cells may play a role in tolerance induction to heart allografts in NHPs. Work is in progress to further characterize these novel cells.
To cite this abstract in AMA style:Morrissette JA, Pruner K, Lee S, Paster J, Sommer W, O J, Hanekamp I, Sage P, Benichou G, Madsen JC. Characterization of a Novel CD8+ B Cell Subset in Monkeys Tolerant of Heart Allografts [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/characterization-of-a-novel-cd8-b-cell-subset-in-monkeys-tolerant-of-heart-allografts/. Accessed March 4, 2021.
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