Current models of B lymphocyte biology posit that B cells continuously recirculate between lymphoid organs, without accumulating in peripheral healthy tissues. Nevertheless, B lymphocytes are one of the most prevalent leukocyte populations in the naive murine heart. To investigate this apparent inconsistency in the literature, we conducted a systematic analysis of myocardial B cell ontogeny, trafficking dynamics, histology, and gene expression patterns. We found that myocardial B cells represent a subpopulation of circulating B cells that make close contact with the microvascular endothelium of the heart and arrest their transit as they pass through the heart. The vast majority (>95%) of myocardial B cells remain intravascular, whereas few (<5%) myocardial B cells cross the endothelium into myocardial tissue. Analyses of mice with B cell deficiency or depletion indicated that B cells modulate the myocardial leukocyte pool composition. Analysis of B cell–deficient animals suggested that B cells modulate myocardial growth and contractility. These results transform our current understanding of B cell recirculation in the naive state and reveal a previously unknown relationship between B cells and myocardial physiology. Further work will be needed to assess the relevance of these findings to other organs.
Bibliographical noteFunding Information:
The authors would like to acknowledge Marco Colonna and Ali Ellebedy for their thoughtful advice and their critical review of the manuscript and Deepta Bhattacharya for his thoughtful advice. This study was supported by research funds from the NIH (R01 HL-58081, HL-73017-0, HL-089543-01, HL 111094, R00 HL138163, T32 HL007081, S10OD020136, and 1K08HL145108-01A1), institutional funds from the Center for Cardiovascular Research at Washington University School of Medicine, and a pilot grant from the McDonnell Genome Institute at Washington University. The authors acknowledge the Washington University Digestive Disease Research Center Morphology Core (National Institute of Diabetes and Digestive and Kidney Diseases, P30 DK052574) for preparing the WGA histology specimens, and Erica Lantelme and the Washington University Flow Cytometry & Fluorescence Activated Cell Sorting Core for assistance with FACS analysis and cell sorting. The manuscript was edited by the Scientific Editing Service supported by the Institute of Clinical and Translational Sciences at Washington University (NIH CTSA grant UL1 TR002345).
© 2020, American Society for Clinical Investigation.