Integrins in engraftment of ex vivo generated plasma cells

Plasma cells (PCs) are terminally differentiated B cells that are long-lived and have high rates of protein secretion. Because of these features, ex vivo generated PCs are being developed as therapeutics for long-term protein delivery. Here, we used proteomics and flow cytometry-based approaches to comprehensively interrogate the surface proteome of activated B cell versus PC populations. Next, we analyzed adhesion proteins that might facilitate engraftment of ex vivo generated PCs at candidate immune sites. We identified key adhesion proteins including integrin alpha 4 (ITGA4) and ITGB1 that were highly expressed on PCs and activated B cells. At steady state, ITGB1 preferentially paired with ITGA4 preventing the pairing of ITGA4 and ITGB7. This phenotype was unique to human versus mouse PCs, indicating a species-specific pattern of integrin expression. Despite high expression on human PCs, ITGB1 was dispensable for human PC BM engraftment but partially required for murine PC engraftment. To investigate the role of integrins in directing localization of murine PCs to specific organs, we generated PCs that expressed high levels of ITGA4, ITGB1, and/or ITGB7. We observed localization of PCs expressing high levels of these integrins to lymphoid and nonlymphoid organs in the peritoneum. Taken together, our findings identify surface proteins on human PCs and showcase PC targeting to peritoneal tissues allowing for potential delivery of therapeutic drugs within the abdominal cavity.