Recent evidence shows that the naïve heart harbors a population of intravascular recirculating B cells that make close contact with the microvascular endothelium of the heart and arrest their transit as they pass through the heart. However, the timing of their appearance and their organ specificity remain unknown. To address this knowledge gap, we performed a systematic analysis of B cells isolated from the myocardium and other organs, from embryonic life to early adulthood. We found that B cells are present in the developing heart by day E13.5. The phenotype of myocardial B cells changed dynamically during development. While neonatal heart B cells were mostly CD11b+ and CD11b-CD21-CD23-, adult B cells were predominantly CD11b-CD21+CD23+. Histological analysis and intravital microscopy of lung and liver showed that organ-associated B cells in contact with the microvascular endothelium were not specific to the heart. Flow cytometric analysis of perfused hearts, livers, lungs and spleen at different developmental stages showed that the dynamic changes in B cell subpopulations observed in the heart during development mirrored changes observed in the spleen, peripheral blood and other organs. Single cell RNAseq analysis of B cells showed that myocardial-associated B cells were part of a larger population of organ-associated B cells that had a distinct gene expression profile. These findings broaden our understanding of the biology of myocardial-associated B cells and suggest that current models of the dynamics of naïve B cell during development are incomplete.
Cibele Rocha-Resende, Wei Yang, Wenjun Li, Daniel Kreisel, Luigi Adamo, Douglas Mann