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Updated: Mar 27, 2026
Flow Cytometry-Based Quantification and Analysis of Myocardial B-Cells
Published on: August 17, 2022
Full Expression of Cardiomyopathy Is Partly Dependent on B-Cells: A Pathway That Involves Cytokine Activation,
Andrea M Cordero-Reyes1, Keith A Youker2, Alejandro R Trevino3
1Houston Methodist DeBakey Heart & Vascular Center, Houston, TX (A.M.C.R., K.A.Y., J.H.F.A., C.M.O., A.B., J.D.E., G.T.A.) Houston Methodist Hospital Research Institute, Houston, TX (A.M.C.R., K.A.Y., D.J.H., J.D.E., G.T.A.) Colegio de Ciencias de la Salud, Escuela de Medicina, Universidad San Francisco de Quito, Quito, Ecuador (A.M.C.R.).
Insights
B-cells contribute to heart failure (HF) progression. Depleting B-cells in a mouse model reduced cardiac damage and preserved heart function, indicating their detrimental role in HF.
Area of Science:
- Immunology
- Cardiology
- Pathophysiology
Background:
- Limited data exists on B-cell roles in heart failure (HF) progression.
- Failing human hearts show complement activation and anticardiac antibodies.
- This study investigates B-cell contributions to HF using a non-surgical mouse model.
Purpose of the Study:
- To determine the role of B-cells in the progression of nonischemic cardiomyopathy (CMP).
- To investigate the impact of B-cell depletion on cardiac function and pathology in a HF model.
Main Methods:
- A non-surgical mouse model of cardiomyopathy was induced using l-NAME, NaCl, and angiotensin-II infusion.
- Mice groups included wild-type (WT), severe combined immunodeficiency (SCID; T- and B-cell deficient), CD22(-) (B-cell depleted), and Nude (T-cell deficient).
- B-cell depletion and reconstitution protocols were employed, with analyses including cardiac MRI, gene expression, and histology.
Main Results:
- B-cell depletion (CD22(-) CMP) significantly reduced cardiac cell hypertrophy and collagen deposition, preserving ejection fraction compared to WT CMP.
- B-cell reconstitution in SCID mice restored the CMP phenotype.
- Myocardial IgG3 deposition and apoptosis correlated with CMP development; activated B-cells stimulated cardiac fibroblast collagen production in vitro.
Conclusions:
- Absence of B-cells in this HF model led to reduced hypertrophy, collagen deposition, and preserved left ventricular function.
- B-cell absence correlated with decreased proinflammatory cytokines, immunoglobulin G deposition, and apoptosis.
- These findings suggest B-cells play a contributory role in angiotensin-II-induced heart failure progression.
Background:
Limited information exists on the role of B-cell-dependent mechanisms in the progression of heart failure (HF). However, in failing human myocardium, there is evidence of deposition of activated complement components as well as anticardiac antibodies. We aimed to determine the contribution of B-cells in HF progression using a nonsurgical mouse model of nonischemic cardiomyopathy (CMP).
Methods And Results:
CMP protocol involved the use of l-NAME and NaCl in the drinking water and angiotensin-II infusion for 35 days. At day 35, mice were analyzed by cardiac magnetic resonance imaging, gene expression, and histology. Mice (12 weeks old) were divided into 4 groups, all in C57BL/6 background: wild-type (WT) CMP; severe combined immunodeficiency (SCID) CMP (T- and B-cell deficient); CD22(-) CMP (B-cell depleted); and Nude CMP (T-cell deficient), with their respective controls. We performed B-cell depletion and reconstitution protocols. The protective effect of B-cell depletion was demonstrated by a significant reduction of cell hypertrophy and collagen deposition and a preserved ejection fraction in the CD22(-) CMP group compared to WT CMP. Once SCID mice underwent B-cell reconstitution with isolated CMP B-cells, the CMP phenotype was restored. Furthermore, deposition of IgG3 and apoptosis in the myocardium follows the development of CMP; in addition, in vitro studies demonstrated that activated B-cells stimulate collagen production by cardiac fibroblasts.
Conclusions:
The absence of B-cells in this model of HF resulted in less hypertrophy and collagen deposition, preservation of left ventricular function, and, in association with these changes, a reduction in expression of proinflammatory cytokines, immunoglobulin G deposition, and apoptosis in the myocardium. Taken together, these data suggest that B-cells play a contributory role in an angiotensin-II-induced HF model.
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