Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: The development and maintenance of peripheral tolerance is required for long term success of solid organ transplantation without immuno-suppressive drugs. Using a novel, post-transplant, mixed chimerism-tolerance induction regimen in a Rhesus Macaque (RM) model of kidney transplantation, using total lymphoid irradiation (TLI) and bone marrow transplantation (BMT), we observed a correlation between the generation of donor and recipient cell-chimerism with graft survival. Furthermore, an Interleukin 35 (IL35) expressing regulatory B cell (Breg) is over expressed in long term surviving animals on this regimen. We set out to explore whether IL35 expressing Bregs are part of a potential mechanism associated with immune tolerance.
*Methods: Isolated peripheral blood mononuclear cells (PBMCs) from blood draws of 5 transplant recipient animals on the kidney+TLI+BMT regimen following recovery of lymphocytes (40 days post-transplant), were stained with various fluorochrome conjugated antibodies and used in multi-parameter flow cytometry.
*Results: We found that Breg lymphocyte populations (CD3neg,CD20+, CD24+, CD27+) are dramatically over expressed (42% of CD20+ B cells) in long term graft survival animals vs healthy controls (0.8% of CD20+ B cells) or transplant animals that never attained chimerism (0.6% of CD20+B cells). Furthermore, an increase in IL35+ Bregs (CD3neg,CD20+, CD24+, CD27+,Ebi3+, p35+), was associated with chimerism and increased long term graft survival (50% of CD20+ Bregs in chimeric animals vs 0.3% of Bregs in non-chimeric animals).
*Conclusions: These preliminary findings support further investigation into the potential role that IL35+ Bregs play in chimerism associated immune tolerance. As a potential component of a mechanism for establishing an anti-inflammatory milieu promoting tolerance over inflammation, the knowledge gained from continued investigations of IL35+ Bregs will provide tremendous insight into not just transplantation immunology, but also to auto-immune and chronic inflammatory diseases.
To cite this abstract in AMA style:Sullivan JA, Fechner JH, Jankowska-Gan E, Burlingham WJ, Kaufman DB. Investigation of Il35 Expressing Regulatory B Cells in Tolerance of Kidney Transplantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/investigation-of-il35-expressing-regulatory-b-cells-in-tolerance-of-kidney-transplantation/. Accessed March 8, 2021.
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