*Purpose: BCMA(TNFRSF17) belongs to tumor necrosis factor receptor superfamily. It is selectively expressed during B/plasma cell differentiation while being nearly absent on naive and memory B cells. Therefore, BCMA may serve as a highly selective antigen for mature B-cell targeting. The current study investigated BCMA expression by peripheral B cells and plasma cells during the development of de novo alloantibody responses.

*Methods: A mouse model of allo-sensitization induced by skin allograft was used to study BCMA expression by B cell subsets and plasma cells. Blood samples were collected weekly for measurement of anti-HLA.A2 IgM and IgG titers. PBMCs and splenic lymphocytes were analyzed in FACS for identification of B cell subsets expressing surface BCMA. Splenic B-cells were isolated using EasySep B-cell isolation kit. mRNA expression of TNFRSF17 was studied in quantitative PCR.

*Results: qPCR demonstrated a significant increase in TNFRSF17 mRNA expression by splenic B-cells isolated from HLA.A2 sensitized mice (p=0.004 vs. naïve control). Multi-parameter FACS analysis of splenic lymphocytic cells showed that cell surface BCMA (CD269) was expressed by the majority of CD38⁺CD138⁺ plasma cells (60-80%), and by members of CD19⁺CD23⁺sIgD⁺ mature B-cells. CD269 was minimally expressed by early transitional B-cells (CD93⁺/CD19⁺/CD23^–). Following skin grafting BCMA was increasingly expressed on mature B cells and plasma cells at Days 14 (p=0.03 vs. naïve control mice), 21(p=0.004) and 28(p=0.0001) PTx. Increase in BCMA expression by B cells was associated with high DSA IgG titers in the blood, indicating plasmablast differentiation.

*Conclusions: Our data demonstrate that BCMA is increasingly expressed by B/plasma cells during the development of alloantibody responses. Thus, targeting BCMA may serve as a new treatment strategy for desensitization in HLA highly sensitized transplant patients.

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