Abstract Number: PB0960
Meeting: ISTH 2021 Congress
Background: Platelet alloimmunization remains a potentially serious adverse transfusion event. Alloantibodies produced by the recipient, mainly directed against HLA I donor antigens, can compromise the therapeutic efficiency of upcoming transfusion and may lead to refractoriness. The cellular mechanisms regulating this process are not yet identified. We hypothesize that the cell types involved could be found in the splenic environment where alloimmune response takes place. Within the spleen, the marginal zone B cells (MZB) represent attractive candidates as they are known to rapidly react to blood-borne antigens.
Aims: To assess the role of the MZB in platelet alloimmune response and the associated refractory state.
Methods: Balb/C (H2d) mice were transfused weekly with platelets isolated from C57Bl6/J mice (H2b) during 3 weeks. Alloantibody production (anti-H2b) was evaluated by flow cytometry. To evaluate the role of MZB, mice were either treated with a combination of depleting anti-CD11a/CD49d antibodies, or with FTY720, a S1P1-receptor antagonist that prevents the proper localization of MZB in the marginal zone.
Results: H2b-platelets transfused weekly in Balb/C mice led to anti-H2b alloantibody production from the second week. When Balb/C mice were depleted in MZB or treated with FTY720, alloantibody production was significantly reduced in both cases as compared to control mice. To determine whether this alloantibody production could lead to a refractory state, alloimmunized mice were transfused with ex vivo CFDA-SE/oregon green labelled H2b-platelets. After 2 hours, transfused platelets were all eliminated from the circulation of the recipient. Interestingly, following MZB-immunodepletion or FTY720-treatment, transfused platelets were still found in the circulation after 24h, suggesting that the reduction of alloantibody production may prevent the associated refractory state.
Conclusions: This study suggests that targeting MZB cells could be a new therapeutic strategy to minimize platelet alloimmunization and prevent the associated refractory state.
To cite this abstract in AMA style:Couvidou A, Angenieux C, Ruch L, Gachet C, Maitre B. Identification of Marginal Zone B Cells as Key Players in a Mouse Model of Platelet Alloimmunization [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/identification-of-marginal-zone-b-cells-as-key-players-in-a-mouse-model-of-platelet-alloimmunization/. Accessed September 16, 2021.
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