AABB22: Marginal Zone B Cells Are Responsible for Alloantibody Production Following Platelet Transfusion in Mice

Findings presented at the 2022 AABB Annual Meeting suggest that targeting marginal zone B (MZB) cells prevents alloimmunization following platelet transfusions and the associated refractory state. Adèle Couvidou, PhD candidate at the Université de Strasbourg in France, presented the findings during Sunday’s Plenary Oral Abstract Session.

Couvidou and her co-investigators hypothesized that the cell types involved in platelet alloimmunization could be found in the splenic environment where alloimmune response takes place. Because MZB cells are involved in alloimmunization against red blood cells, investigators focused on those cells.

To evaluate the role of MZB cells in platelet alloimmunization, Couvidou and her co-investigators set up a murine model of platelet alloimmunization, transfusing platelets from H2^B mice to H2^D mice weekly for three weeks. This led to anti-H2^b antibody production.

After harvesting the spleen, investigators detected most transfused platelets in the red pulp, but found that 20% were located in the marginal zone. Within the marginal zone, investigators focused on CD21-positive cells corresponding to MZB cells and detected colocalization between the MZB cells and transfused platelets.

Investigators utilized two strategies to identify whether this interaction was important for alloimmunization. First, they immunodepleted MZB cells by injecting recipient mice with a cocktail of anti-CD11a/-CD49d antibodies. Compared to control mice, MZB cell-depleted mice had significantly lower antibody levels, indicating that MZB cells can be involved in platelet alloimmunization.

To confirm the results, Couvidou and her co-investigators displaced MZB cells from the marginal zone a using FTY720, a S1P1 antagonist. Like the MZB-depleted mice, those treated with FTY720 had lower antibody levels compared to control mice. “Overall, these results indicate that marginal zone B cells are implicated in platelet alloimmunization,” Couvidou said.

To determine whether targeting MZB cells could prevent subsequent refractoriness, investigators transfused platelets to the previously alloimmunized mice, naïve mice, MBZ-depleted mice and FTY720-treated mice. At 2 hours post-transfusion, platelets were still detectable in naïve mice but not in alloimmunized mice. Both MBZ-depleted mice and FTY720-treated mice were protected from platelet refractoriness.

Couvidou and her co-investigators believe the results may open up new pharmacological perspectives to prevent alloimmunization and immune refractory state.