Circulating T Follicular Helper Proliferation And Memory B Cell Activation Correlate With Donor Specific Allo-antibody Occurrence And Antibody-mediated Rejection After Kidney Transplantation
1Surgery, University of Pittsburgh, Pittsburgh, PA, 2Inserm Unité mixte de recherche 1160, Paris, France
Meeting: 2019 American Transplant Congress
Abstract number: 56
Keywords: B cells, HLA antibodies, Kidney transplantation, T helper cells
Session Information
Session Name: Concurrent Session: Biomarkers, Immune Monitoring and Outcomes I
Session Type: Concurrent Session
Date: Sunday, June 2, 2019
Session Time: 2:30pm-4:00pm
Presentation Time: 2:54pm-3:06pm
Location: Room 306
*Purpose: Crosstalk between T follicular helper (Tfh) cells and B cells is necessary for class-switched antibody generation. The contribution of memory Tfh and B cells to humoral response after transplantation is unclear.
*Methods: Using 22-color spectral flow cytometry, we evaluated the immunophenotype and the function of circulating (c)Tfh and memory (m)B cells from 65 Kidney Transplant (KTx) recipients consisting of : (i) donor specific allo-antibody positive (DSA+) free of antibody-mediated rejection (ABMR) (n=24) at the time of DSA occurence, (ii) DSA+ at the time of biopsy-proven ABMR (n=16) and (iii) DSA- patients, free of DSA or rejection (n=25), as controls.
*Results: We identified a subset of Ki67+ (proliferating) cTfh (CD4+ CD45RO+ CXCR5+) that was significantly expanded in DSA+ patients at the time of DSA occurrence as compared to DSA- patients (P<0.0001). This proliferating cTfh subset from DSA+ patients expressed higher levels of activation marker CD38 (P<0.0001), co-stimulation molecules ICOS (P<0.0001) and CD28 (P<0.0001) and resembled germinal center Tfh, with increased expression of Irf4 (P=0.02) and IL-21R (P<0.0001) as compared to DSA- patients. Concomitantly, a subset of activated mB cells (CD19+CD27+CD21-) was also significantly expanded at the time of DSA occurrence (P<0.0001). The expansion of activated mB cells was associated with increased levels of double negative mB (CD27-CD21-) and decreased levels of resting mB subset (CD27+CD21+) in DSA+ patients as compared to DSA- patients (P<0.0001 for both). There was a positive correlation between Ki67+cTfh and CD19+CD27+CD21- mB cells (R2=0.21, P=0.0002) in DSA+ patients. Moreover, both Ki67+cTfh and CD19+CD27+CD21- mB cells levels were the highest in ABMR patients than in DSA+ patients free of ABMR (P=0.01, P=0.02 respectively). To evaluate ex vivo the functional potential of cTfh and mB cells, we FACS-sorted cTfh and mB cells and placed them in co-culture for 6 days in presence or absence of staphylococcal enterotoxin B (SEB). Our results show that while cTfh from all KTx patients triggered plasmablast formation, the IgG production after 6 days of co-culture was significantly higher in DSA+ and ABMR patients than in DSA- patients (P=0.02).
*Conclusions: Our findings show that during an ongoing DSA response after KTx, cTfh are proliferating and functional, triggering mB cell activation and antibody production. Therapeutic intervention targeting Tfh-B interaction may represent an important strategy to prevent DSA formation and ABMR occurence.
To cite this abstract in AMA style:
Louis K, Macedo C, Marrari M, Ramaswami B, Lucas M, Elinoff B, Yamada M, Gu X, Chalasani G, Zeevi A, Randhawa P, Lefaucheur C, Metes D. Circulating T Follicular Helper Proliferation And Memory B Cell Activation Correlate With Donor Specific Allo-antibody Occurrence And Antibody-mediated Rejection After Kidney Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/circulating-t-follicular-helper-proliferation-and-memory-b-cell-activation-correlate-with-donor-specific-allo-antibody-occurrence-and-antibody-mediated-rejection-after-kidney-transplantation/. Accessed May 18, 2025.« Back to 2019 American Transplant Congress