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Myocardial B cells are a subset of circulating lymphocytes with delayed transit through the heart
Luigi Adamo, … , Gwendalyn J. Randolph, Douglas L. Mann
Luigi Adamo, … , Gwendalyn J. Randolph, Douglas L. Mann
Published January 16, 2020
Citation Information: JCI Insight. 2020;5(3):e134700. https://doi.org/10.1172/jci.insight.134700.
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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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