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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 3

Myocardial B cells are mostly intravascular and in intimate contact with the endothelium.

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Myocardial B cells are mostly intravascular and in intimate contact with...
(A) Confocal imaging of a section of myocardial tissue from a CD19-tdTomato reporter animal. The 3-dimensional reconstruction of multiple images acquired along the z axes shows that B cells are distributed throughout the myocardium. LSM 880 Indimo, AxioObserver Zeiss Microscope using a Plan-Apochromat 10×/0.8 M27 objective. Z-stack of 69 slices (64.829 uM). (B–E) Confocal images of a frozen section of murine myocardium. CD19-tdTomato, red; CD31, green; DAPI, blue. Myocardial B cells are mostly intravascular and in intimate contact with the endothelium. Taken with an LSM 880 Indimo, AxioObserver Zeiss Microscope using a Plan-Apochromat 63×/1.3 oil DIC UV-IR M27 objective and 2× digital zoom (B). Some B cells are in pairs. Taken with an LSM 880 Indimo, AxioObserver Zeiss Microscope using a Plan-Apochromat 40×/1.3 oil DIC UV-IR M27 objective and a 2.2 digital zoom (C). Few B cells are found in the intraparenchymal/extravascular space, as singlets or doublets. taken with an Olympus Fluoview FV1000 using a PLAPON 60× NA1.4 objective and 2× digital zoom (D); rare B cells are found in transit through the endothelium, taken with the same microscope and objective as D but it is a Z-stack of 23 slices, 0.46 uM/slice (E). (F) Flow cytometric analysis of myocardial CD19+CD45+ cells 3 minutes after i.v. injection of a CD45.2 antibody. Most myocardial B cells are stained by the i.v. injected antibody, confirming their intravascular location. Only about 3% of cells are not stained by the antibody and are, therefore, extravascular. The flow cytometry plot is representative of 3 independent experiments. Percentage of total CD19+ cells is reported next to each gate. The bar graph reports mean percentage of extravascular CD19+ cells ± SD.

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