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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 5

B cell deficiency alters the myocardial leukocyte pool, reduces myocardial mass, and alters left ventricular contractility.

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B cell deficiency alters the myocardial leukocyte pool, reduces myocardi...
(A) Flow cytometry analysis of myocardial leucocytes in WT and μMT mice. μMT mice have less Ly6C+ cells and more CD4+ and CD8+ T cells. (B). Flow cytometric analysis of WT animals depleted of B cell through administration of anti-CD20 antibody or isotype control. Antibody-mediated B cell depletion is associated with an increase in Ly6G+ cells (P = 0.056), CD4+ and CD8+ cells. (C) Analysis of hearts from 27-week-old C57/B6J mice and syngeneic age/sex-matched μMT mice showed that μMT mice have myocardial fibers with smaller cross-sectional area as assessed by WGA staining. Representative images of WGA staining for each group are shown and cumulative data are reported. (D) μMT mice have lower myocardial mass as assessed by heart weight/tibia length (mg/mm). (E) Echocardiographic analysis of left ventricular function in WT mice and matched μMT mice. μMT mice have higher left ventricular ejection fraction (LVEF) and faster ventricular relaxation (dV/dT-d, volume change per unit of time during diastolic relaxation; ESV, end-systolic volume). (F) Flow cytometry analysis of a sample of human myocardium collected at the time of implantation of a left ventricular assist device and dissociated enzymatically. A clear population of CD19+ cells is shown. Representative plot from 3 heart samples analyzed. Percentage of myocardial CD45+ cells is reported next to the gate. (G) Histological analysis of human myocardium collected at the time of LVAD placement shows that, similarly to the murine heart, the human heart harbors B cells in the intravascular space, in intimate contact with the endothelium. Magnification, 40×. Pairwise comparisons were performed with 2-tailed t test. Data are expressed as average ± SD. The WT and μMT groups were compared using unpaired 2-tailed t test adjusted for multiple comparisons with the FDR method in A and B. In C, the 2 groups were compared using nested t test *P < 0.05. **P < 0.01.

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