B cells dominate the heart immune infiltrate during chronic infectious cardiomyopathy

Recent advances in single-cell and spatially resolved multi-omics have revolutionised our understanding of the cellular and molecular niches governing cardiac homeostasis and acute injury. However, the immune-stromal networks sustaining long-term, chronic heart pathology remain poorly defined, largely due to a paucity of physiologically relevant experimental models. Here, through a side-by-side multi-omic comparison of Trypanosoma cruzi-infected mouse models displaying contrasting degrees of chronic myocardial pathology and fibrosis, we define the long-term cellular landscape of the inflamed fibrotic heart. We reveal that class-switched, antibody-secreting plasma B cells represent the predominant immune subset infiltrating the fibrotic myocardium. CellChat intercellular communication modelling identifies plasma cell-fibroblast crosstalk as the strongest immune-stromal interaction in the fibrosis-prone heart, driven by predicted matrix anchoring (CD44-collagen/laminin) and molecular survival axes (App-Cd74, C3-Cr2). Supporting these computational predictions, immunofluorescence and spatial profiling confirm close proximity between plasma B cells and fibroblasts, alongside a striking accumulation of B cells embedded within extracellular matrix-rich cardiac scars. This localised B cell response maintains prominent pools of parasite-reactive and heart-autoreactive antibody-secreting cells despite a lack of detectable parasite signal in their immediate micro-vicinity. Together, these findings identify a matrix-associated plasma B cell-fibroblast niche as a central driver of chronic cardiac remodelling, revealing how persistent tissue scarring can become decoupled from direct local pathogen presence.