Alloreactive B Cells in Transplant Tolerant Recipients Cannot Differentiate into Antibody-Secreting Cells but Can Suppress Donor-Specific IgG Production By Naïve B Cells
1Department of Surgery, Section of Transplant, University of Chicago, Chicago, IL, 2Department of Medicine, University of Chicago, Chicago, IL
Meeting: 2019 American Transplant Congress
Abstract number: 623
Keywords: Alloantibodies, B cells, Immunoglobulins (Ig), Tolerance
Session Information
Session Time: 8:30am-10:00am
Presentation Time: 9:15am-9:30am
Location: Veterans Auditorium
*Purpose: Donor specific transplantation tolerance has long been the goal of clinical transplantation. Clinical observations suggest that donor-specific antibodies (DSA) are a major cause of graft rejection despite ongoing immunosuppression, leading us to hypothesize that stable transplantation tolerance requires donor-specific B cell responses to also be profoundly suppressed. We hypothesize that this can be achieved by the control of T cell help to B cells, and also through the induction of B cell-intrinsic tolerance. The objective of this studies is to define how donor-MHC-specific B cells are constrained in experimental model of transplantation tolerance.
*Methods: We used a well-established experimental model of transplantation tolerance induced to allogeneic B/c hearts with anti-CD154+ donor spleen cell transfusion. In addition, to test whether tolerant B cells could be rescued by ongoing germinal centre (GC) responses, we adoptively transferred tolerant B cells (CD45.2, Igha) into congenic CD45.1/IgHb hosts, followed by B/c or C3H spleen cell immunization and then measured the alloantibodies at day 21 post-adoptive transfer.
*Results: We observed that donor-specific B cells are intrinsically tolerant. B cells from tolerant recipients did not produce αB/c IgG when adoptively transferred into naïve MD4 host (~95% of B cells are specific for HEL) and then challenged with B/c spleen cells. We showed that the tolerant B cells were defective in their ability to differentiate into germinal center (GL7+Fas+) B cells. In addition, we also showed that tolerant B cells did not recover their ability to differentiate into antibody secreting cells. In fact, congenic hosts of tolerant B cells produced significantly reduced anti-B/c IgG compared to congenic hosts of naïve B cells. Finally, the ability of tolerant B cells to suppress host IgG production was donor-specific, as congenic host receiving tolerant B cells produced comparable IgG to third-party (C3H) splenocyte immunization.
*Conclusions: Taken together, our data demonstrate that tolerant donor-specific B cells are profoundly altered compared to naïve B cells: they have significantly diminished ability to differentiate into germinal center and antibody secreting cells, but acquired the ability to suppress donor-specific, but not third-party, antibody responses by naïve B cells.
To cite this abstract in AMA style:
Khiew SH, Chen J, Jain D, Wang Q, Yin D, Alegre M, Chong AS. Alloreactive B Cells in Transplant Tolerant Recipients Cannot Differentiate into Antibody-Secreting Cells but Can Suppress Donor-Specific IgG Production By Naïve B Cells [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/alloreactive-b-cells-in-transplant-tolerant-recipients-cannot-differentiate-into-antibody-secreting-cells-but-can-suppress-donor-specific-igg-production-by-naive-b-cells/. Accessed May 11, 2025.« Back to 2019 American Transplant Congress