Human B-cells can form Hetero-aggregates with Blood Platelets: A Novel Insight into Adaptive Immunity Regulation in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation and neurodegeneration. Our original study analyzes the interactions between blood platelets and leukocytes in MS, focused on their potential role in modulating immune responses. We demonstrated, for the first time, a significant increase in leukocyte migration towards platelets, indicating their higher chemotactic capabilities in MS. This novel finding is supported by microscopic imaging of platelet-leukocyte hetero-aggregates (PLAs). Our study included platelet activation status and platelet-lymphocyte cross-talk analysis distinguishing lymphocytic subpopulation in patients with relapsing-remitting (RRMS) and secondary progressive MS (SPMS) compared to healthy controls (HC). Flow cytometry method revealed an elevated expression of platelet activation typical markers i.e. PAC-1 and CD62P in both phenotypes of MS, especially in RRMS, and higher GPVI level in SPMS. Detailed immunophenotyping and confocal imaging showed an increased pool of platelet-lymphocyte aggregates (PLAs-Ly), particularly involving B-cells over T-cells across both MS phenotypes. The study also explored the involvement of the CD40-CD40L pathway, discovering significant correlations between platelet CD40L expression and lymphocytic antigen CD40, especially on B-cells in SPMS. This novel finding may indicate the special significance of platelet-B-cell cross-talk in progressive disease phenotype. Our research identified potential platelet-leukocyte interaction pathways that may influence the lymphocyte-mediated immune response in MS, highlighting the unexplored formation of platelet-B cell hetero-aggregates (PLAs-LyB).