Developmental changes in myocardial B cells mirror changes in B cells associated with different organs
Cibele Rocha-Resende, Wei Yang, Wenjun Li, Daniel Kreisel, Luigi Adamo, Douglas L. Mann
Cibele Rocha-Resende, Wei Yang, Wenjun Li, Daniel Kreisel, Luigi Adamo, Douglas L. Mann
View: Text | PDF
Research Article Cardiology Immunology

Developmental changes in myocardial B cells mirror changes in B cells associated with different organs

Abstract

The naive heart harbors a population of intravascular B cells that make close contact with the cardiac microvasculature. However, the timing of their appearance and their organ specificity remain unknown. To address this knowledge gap, we performed a systematic analysis of B cells isolated from the myocardium and other organs, from embryonic life to adulthood. We found that the phenotype of myocardial B cells changed dynamically during development. While neonatal heart B cells were mostly CD11b+ and CD11b– CD21–CD23–, adult B cells were predominantly CD11b–CD21+CD23+. Histological analysis and intravital microscopy of lung and liver showed that organ-associated B cells in contact with the microvascular endothelium were not specific to the heart. Flow cytometric analysis of perfused hearts, livers, lungs, and spleen showed that the dynamic changes in B cell subpopulations observed in the heart during development mirrored changes observed in the other organs. Single cell RNA sequencing (scRNAseq) analysis of B cells showed that myocardial B cells were part of a larger population of organ-associated B cells that had a distinct transcriptional profile. These findings broaden our understanding of the biology of myocardial-associated B cells and suggest that current models of the dynamics of naive B cells during development are incomplete.

Authors

Cibele Rocha-Resende, Wei Yang, Wenjun Li, Daniel Kreisel, Luigi Adamo, Douglas L. Mann

×

Figure 2

Transcriptional profiling identifies myocardial B cells as a heterogeneous, dynamic population of transitional, follicular, and B1 cells.

Options: View larger image (or click on image) Download as PowerPoint
Transcriptional profiling identifies myocardial B cells as a heterogeneo...
(A) A 10× sequencing analysis of CD45+Aqua–CD19+ cells sorted from the heart of neonatal (2 week old) and adult (8 week old) mice. Neonatal and adult cardiac B cells show a distinct transcriptional profile. (B) Subsets of B cells from neonatal and adult myocardium. Cardiac B cells were stained with TotalSeq antibodies for CD11b, CD23, and CD21 before sequencing. Comparison of this UMAP plot with the UMAP plot reported in A shows that CD21+CD23+ cells are mostly found in the adult heart, while CD21–CD23– are mostly neonatal. (C) Differentially expressed genes between B cell subsets were used to generate hypothetical developmental relationships using Monocle algorithms. Pseudotime analysis indicates that CD21–CD23– cells move toward CD21+CD23+ cells. (D–F) Heatmaps reporting the relative expression of the top 20 unique upregulated genes in the CD21–CD23– (D), CD21+CD23+ (E), and CD11b+ (F) myocardial cells within various B cell subtypes catalogued in the Immgen RNAseq database (for details, see Supplemental Table 2). The transcriptional profile of CD21+CD23+ myocardial B cells resembles the transcriptional profile of splenic Transitional 3 (T3) and follicular cells (D). Cardiac CD21–CD23– cluster are similar to T1 and newly formed B cells (BM-NFB) (E). CD11b+ myocardial B cells are transcriptionally similar to B1 cells in the peritoneal cavity (F). Sp, spleen; P, peritoneal; CLP, common lymphoid progenitor; NFB, newly formed B cell; T, transitional; (F), female; FO, follicular; MZ, marginal zone; Mem, memory; GC, germinal center; CB, centroblasts; CC, centrocytes; PB, plasmasblasts; PC, plasma cells.