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Myocardial B cells are a subset of circulating lymphocytes with delayed transit through the heart
Luigi Adamo, Cibele Rocha-Resende, Chieh-Yu Lin, Sarah Evans, Jesse Williams, Hao Dun, Wenjun Li, Cedric Mpoy, Prabhakar S. Andhey, Buck E. Rogers, Kory Lavine, Daniel Kreisel, Maxim Artyomov, Gwendalyn J. Randolph, Douglas L. Mann
Luigi Adamo, Cibele Rocha-Resende, Chieh-Yu Lin, Sarah Evans, Jesse Williams, Hao Dun, Wenjun Li, Cedric Mpoy, Prabhakar S. Andhey, Buck E. Rogers, Kory Lavine, Daniel Kreisel, Maxim Artyomov, Gwendalyn J. Randolph, Douglas L. Mann
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Research Article Cardiology Immunology

Myocardial B cells are a subset of circulating lymphocytes with delayed transit through the heart

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Abstract

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.

Authors

Luigi Adamo, Cibele Rocha-Resende, Chieh-Yu Lin, Sarah Evans, Jesse Williams, Hao Dun, Wenjun Li, Cedric Mpoy, Prabhakar S. Andhey, Buck E. Rogers, Kory Lavine, Daniel Kreisel, Maxim Artyomov, Gwendalyn J. Randolph, Douglas L. Mann

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Figure 1

Myocardial B cells have disparate origin and, for the most part, are not resident cells.

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Myocardial B cells have disparate origin and, for the most part, are not...
(A) Flow cytometric analysis of CD45+CD19+ myocardial cells in a C57/B6J mouse. Most myocardial B cells are CD11b–. Among the CD19+CD11b+ myocardial B cells, the majority are IgM+CD5–, and a small portion are IgM+CD5+. The flow cytometry plots are representative of 3 animals analyzed in different experiments. Mean percentage of total CD19+ cells ± SD is reported next to each gate. (B) Flow cytometric analysis of CD45+CD19+ myocardial cells in C57/B6J B cell–deficient mice (μMT) after BM transplant with WT BM. BM transplant replenished CD11b– cells more efficiently than CD11b+ cells. In the CD11b+ compartment, BM transplant did not produce IgM+CD5+ cells. The flow cytometry plots are representative of 4 animals analyzed in different experiments. Mean percentage of total CD19+ cells ± SD is reported next to each gate. (C) Analysis of myocardial CD45+CD19+ cells from animals conjoined via parabiosis for 3 weeks. Both CD19+CD11b+ and CD19+CD11b– cells showed 50% chimerism, a finding consistent with the observation that myocardial B cells moved freely between animals. Percent chimerism for Ly6G+ neutrophils, CD64+Ly6Clo macrophages, and CD3+ T cells is shown for comparison. (D) Analysis of CD45+CD19+ myocardial B cells in recipient and donor hearts before transplant and on day 4 after heterotopic heart transplant. Before transplant, the heart of the CD45.1 recipient animal contains only CD45.1+ B cells, and the donor heart from a CD45.2 animal contains only CD45.2+ B cells. Four days after transplant, the recipient heart is mostly unchanged, though it contains a small population of CD45.2+ B cells derived from the transplanted heart (left side). The CD45.2 transplanted heart instead has lost almost all of its CD45.2+ B cells and now contains mostly CD45.1+ recipient-derived B cells. Representative flow cytometry plots from 3 independently transplanted animals. Percentage of total CD19+ cells is reported within each gate.

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