Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Our previous study found that B cell maturation antigen (BCMA) is increasingly expressed by B/plasma cells during the development of de novo alloantibody responses. To further evaluate if targeting BCMA may serve as a treatment strategy for HLA desensitization, we currently investigate BCMA expression by B-cells during development of recall alloantibody responses.
*Methods: A mouse model of allogenic re-sensitization was employed, in which a C57BL/6 mouse was immunized by a primary HLA.A2+ skin allograft and re-immunized with a second skin allograft 90 day later. Donor-specific antibody (DSA) were measured using antibody binding assay. BCMA expression by splenic B cell subsets was studied in multicolor flow cytometry.
*Results: Donor-specific (anti-HLA.A2) IgM titers significantly increased at Day 14 (16.5+3.1 MFS, p<0.05 when compared to 11.1+2.3 MFS at Day -1) and Day 21 (15.3+1.9 MFS, p<0.05 when compared to Day -1). The pattern of IgM response is consistent with that observed in de novo IgM response. Recall IgG response is energetic, demonstrating a surge of anti-HLA.A2 IgG at Day 14 (501+170 MFS vs. Day-1 110.8+36.3 MFS, p=0.0004) and a peak DSA IgG titer at Day 21 (740+212 vs. Day-1 p= 0.001). FACS analysis of splenic lymphocytic cells demonstrated that relative population of B220+ B-cells significantly increased from 48.9+2.2% at Day -1(before re-sensitization) to 62.5+2.8% at Day 7 (p=0.006), then peaked at 68.2+1.1% at Day 21 (p=0.0004) post-sensitization. B cells co-expressing BCMA (B220+BCMA+) increased by 2 folds from 14.6+6% at Day -1 to 30.3+2.6% at Day 14 (p=0.005) and 32.2+1.3% at Day 21(p=0.0006). In addition, B-cell subsets expressing CD23 phenotype significantly increased from 32+2.8% at Day-1, to 43+1.6% at Day 7 (p=0.008), 47.8+2.5% at Day 14 (p=0.001) and 48.6+3% at Day 21(p=0.004) whereas BCMA expression by CD23+ subset increased from 11+1% to 27+4% at Day 21 (p=0.0038), indicating progress in B-cell maturation.
*Conclusions: DSA generated in recall responses are coupled with dynamic B-cell propagation and increased BCMA expression in the spleens. Therefore, targeting BCMA-expressing alloreactive B-cells may serve as a desensitization strategy for organ transplant patients, especially those highly HLA sensitized individuals.
To cite this abstract in AMA style:Wu G, Kim I, Chai N, Klein A, Jordan S. Increasing Expression of B-cell Maturation Antigen during the Development of Recall Antibody Responses: A Prospective Pharmaceutical Target for B-cell Suppression? [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/increasing-expression-of-b-cell-maturation-antigen-during-the-development-of-recall-antibody-responses-a-prospective-pharmaceutical-target-for-b-cell-suppression/. Accessed September 25, 2021.
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