Session Time: 9:59am-10:40am
Presentation Time: 10:30am-10:37am
Location: Main Channel
*Purpose: Alloantibodies produced by recipient B cells are associated with rejection after intestinal transplantation (ITx) and negatively impact patient and graft survival. However, the dynamics of recipient B cell repopulation of intestinal allografts, their phenotypic changes, and their roles in mediating rejection locally within the allograft are not yet defined. We hypothesized that the early kinetics of gut tissue resident B cell replacement may shape local and systemic recipient B cell responses after ITx, including donor-specific antibody (DSA) development and allograft rejection.
*Methods: Using spectral flow cytometry and B cell receptor (BCR) heavy chain sequencing, immune characterization was performed on serial endoscopic surveillance biopsies of the intestinal allograft and peripheral blood from 7 consenting ITx recipients. Findings were correlated with clinical pathology results and serum DSA.
*Results: In intestinal allografts, recipient B cells replaced graft donor lamina propria B cells over a 15 day – 33 month period. This process tended to be faster in ITx recipients developing DSA in the first 90 days after transplant and in recipients of young (<1 year of age) graft donors. In the first 200 days post-ITx, recipient plasma cells (PCs) appeared in grafts of 2/2 isolated intestinal transplant (iITx) recipients with both cellular rejection and DSA, but in 0/5 multivisceral transplant (MVTx) recipients without both conditions. In an iITx patient with chronic rejection, Luminex single antigen bead testing of cultured recipient B cells and PCs from the graft mucosa identified secreted IgG with a specificity matching one of the DSA detected in serum during rejection. Tracking the recipient BCR repertoire in the graft over time revealed that recipient clones identified in the allograft overlapped more frequently with clones from native GI tract samples than with those from the peripheral blood.
*Conclusions: Rapid repopulation of the intestinal allograft by recipient B cells may be associated with rejection and de novo DSA. Recipient B cells residing within the allograft are a potential local source of DSA and may populate the allograft from GI tract-associated networks. Further identification of recipient B cell specificities and their clonal distribution during rejection may enhance our understanding of how B cells participate in organ-specific alloimmunity in ITx.
To cite this abstract in AMA style:Waffarn E, Fu J, Frangaj K, Meng W, Rosenfeld AM, Li M, Rodgers K, Vasilescu R, Prak ETLuning, Griesemer A, Kato T, Martinez M, Sykes M. Allograft Repopulating Recipient B Cells after Human Intestinal Transplantation and Their Association with Donor Specific Antibody Secretion and Rejection [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/allograft-repopulating-recipient-b-cells-after-human-intestinal-transplantation-and-their-association-with-donor-specific-antibody-secretion-and-rejection/. Accessed October 27, 2020.
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