Skip to main content
SpringerLink
Log in

The Role of B Cells in Cardiomyopathy and Heart Failure

  • Myocardial Disease (A Abbate and M Merlo, Section Editors)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To summarize the current knowledge on the role that B lymphocytes play in heart failure.

Recent Findings

Several studies from murine models have shown that B cells modulate cardiac adaptation to injury and ultimately affect the degree of cardiac dysfunction after acute ischemic damage. In addition, a B cell–modulating small molecule was recently shown to have beneficial effects in humans with heart failure with preserved ejection fraction.

Summary

B lymphocytes are specialized immune cells present in all jawed vertebrates. They are characteristically known for their ability to produce antibodies, but they have other functions and are important players in virtually all forms of immune responses. A growing body of evidence indicates that B cells are intimately connected with the heart and that B cell dysregulation might play a role in the pathogenesis and progression of both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. B cells are therefore gathering attention as potential targets for the development of novel immunomodulatory-based treatments for heart failure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Parra D, Takizawa F, Sunyer JO. Evolution of B cell immunity. Annu Rev Anim Biosci. 2013;1:65–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. LeBien TW, Tedder TF. B lymphocytes: how they develop and function. Blood. 2008;112(5):1570–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chen X, Jensen PE. The role of B lymphocytes as antigen-presenting cells. Arch Immunol Ther Exp (Warsz). 2008;56(2):77–83.

    Article  CAS  Google Scholar 

  4. Fillatreau S. Cytokine-producing B cells as regulators of pathogenic and protective immune responses. Ann Rheum Dis. 2013;72(suppl 2):ii80.

  5. Kantor AB, Herzenberg LA. Origin of murine B cell lineages. Annu Rev Immunol. 1993;11:501–38.

    Article  CAS  PubMed  Google Scholar 

  6. Naradikian MS, et al. Understanding B cell biology. In: Bosch X, Ramos-Casals M, Khamashta MA, editors., et al., Drugs targeting B-cells in autoimmune diseases. Basel: Springer Basel; 2014. p. 11–35.

    Chapter  Google Scholar 

  7. Kawahara T, et al. Peritoneal cavity B cells are precursors of splenic IgM natural antibody-producing cells. J Immunol. 2003;171(10):5406–14.

    Article  CAS  PubMed  Google Scholar 

  8. Yenson V, Baumgarth N. Purification and immune phenotyping of B-1 cells from body cavities of mice. Methods Mol Biol. 2014;1190:17–34.

    Article  CAS  PubMed  Google Scholar 

  9. Montecino-Rodriguez E, Dorshkind K. B-1 B cell development in the fetus and adult. Immunity. 2012;36(1):13–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. •• Adamo L, et al. Modulation of subsets of cardiac B lymphocytes improves cardiac function after acute injury. JCI Insight. 2018;3(11). Findings from this study demonstrate for the first time that small molecule–mediate modulation of B cells improves cardiac function after acute ischemic injury and therefore point at B cells as a viable therapeutic target for the prevention of heart failure after myocardial infarction.

  11. Cerutti A, Cols M, Puga I. Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes. Nat Rev Immunol. 2013;13(2):118–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rajewsky K. Clonal selection and learning in the antibody system. Nature. 1996;381(6585):751–8.

    Article  CAS  PubMed  Google Scholar 

  13. Bos NA, et al. Serum immunoglobulin levels and naturally occurring antibodies against carbohydrate antigens in germ-free BALB/c mice fed chemically defined ultrafiltered diet. Eur J Immunol. 1989;19(12):2335–9.

    Article  CAS  PubMed  Google Scholar 

  14. Palma J, et al. Natural antibodies - facts known and unknown. Cent Eur J Immunol. 2018;43(4):466–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Heesters BA, et al. Antigen presentation to B cells. Trends Immunol. 2016;37(12):844–54.

    Article  CAS  PubMed  Google Scholar 

  16. Diaz M, Casali P. Somatic immunoglobulin hypermutation. Curr Opin Immunol. 2002;14(2):235–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Reth M. Antigen receptors on B lymphocytes. Annu Rev Immunol. 1992;10:97–121.

    Article  CAS  PubMed  Google Scholar 

  18. Kurosaki T, Kometani K, Ise W. Memory B cells. Nat Rev Immunol. 2015;15(3):149–59.

    Article  CAS  PubMed  Google Scholar 

  19. Roche PA, Furuta K. The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol. 2015;15(4):203–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Katkere B, Rosa S, Drake JR. The Syk-binding ubiquitin ligase c-Cbl mediates signaling-dependent B cell receptor ubiquitination and B cell receptor-mediated antigen processing and presentation. J Biol Chem. 2012;287(20):16636–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Adler LN, et al. The other function: class II-restricted antigen presentation by B cells. Front Immunol. 2017;8:319–319.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Duddy ME, Alter A, Bar-Or A. Distinct profiles of human B cell effector cytokines: a role in immune regulation? J Immunol. 2004;172(6):3422–7.

    Article  CAS  PubMed  Google Scholar 

  23. Shen P, Fillatreau S. Antibody-independent functions of B cells: a focus on cytokines. Nat Rev Immunol. 2015;15(7):441–51.

    Article  CAS  PubMed  Google Scholar 

  24. •• Zouggari Y, et al. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nat Med. 2013;19(10):1273–80. Findings from this study demonstrate for the first time a functional connection between B lymphocytes and the heart.

  25. Chousterman BG, Swirski FK. Innate response activator B cells: origins and functions. Int Immunol. 2015;27(10):537–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rosser EC, Mauri C. Regulatory B cells: origin, phenotype, and function. Immunity. 2015;42(4):607–12.

    Article  CAS  PubMed  Google Scholar 

  27. Chimen M, et al. Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease. Nat Med. 2015;21(5):467–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Magee CN, Boenisch O, Najafian N. The role of costimulatory molecules in directing the functional differentiation of alloreactive T helper cells. Am J Transplant. 2012;12(10):2588–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gowans JL, Knight EJ. The route of re-circulation of lymphocytes in the rat. Proc R Soc Lond B Biol Sci. 1964;159:257–82.

    Article  CAS  PubMed  Google Scholar 

  30. Kunkel EJ, Butcher EC. Chemokines and the tissue-specific migration of lymphocytes. Immunity. 2002;16(1):1–4.

    Article  CAS  PubMed  Google Scholar 

  31. Tanaka T, et al. Molecular determinants controlling homeostatic recirculation and tissue-specific trafficking of lymphocytes. Int Arch Allergy Immunol. 2004;134(2):120–34.

    Article  PubMed  Google Scholar 

  32. Adamo L, et al. Modulation of subsets of cardiac B lymphocytes improves cardiac function after acute injury. JCI Insight. 2018;3(11).

  33. Bonner F, et al. Resident cardiac immune cells and expression of the ectonucleotidase enzymes CD39 and CD73 after ischemic injury. PLoS One. 7(4):e34730.

  34. Rocha-Resende C, et al. Developmental changes in myocardial B cells mirror changes in B cells associated with different organs. JCI Insight, 2020;5(16).

  35. Horckmans M, et al. Pericardial adipose tissue regulates granulopoiesis, fibrosis and cardiac function after myocardial infarction. Circulation. 2017.

  36. Wu L, et al. IL-10-producing B cells are enriched in murine pericardial adipose tissues and ameliorate the outcome of acute myocardial infarction. Proc Natl Acad Sci U S A. 2019;116(43):21673–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Adamo L, et al. Myocardial B cells are a subset of circulating lymphocytes with delayed transit through the heart. JCI Insight. 2020;5(3).

  38. • Rocha-Resende C, Pani F, Adamo L. B cells modulate the expression of MHC-II on cardiac CCR2(-) macrophages. J Mol Cell Cardiol. 2021;157:98–103. A large body of literature indicates that cardiac macrophages play an important role in heart failure. Findings from this study show that B cells modulate the phenotype of cardiac macrophage and therefore strengthen the emerging paradigm of a tight connection between B cells and heart failure.

  39. Noutsias M, et al. Phenotypic characterization of infiltrates in dilated cardiomyopathy - diagnostic significance of T-lymphocytes and macrophages in inflammatory cardiomyopathy. Med Sci Monit. 2002;8(7):CR478–87.

  40. Litvinukova M, et al. Cells of the adult human heart. Nature. 2020;588(7838):466–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Yan X, et al. Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction. J Mol Cell Cardiol. 2013;62:24–35.

    Article  CAS  PubMed  Google Scholar 

  42. Heinrichs M, et al. The healing myocardium mobilizes a distinct B-cell subset through a CXCL13-CXCR5-dependent mechanism. Cardiovasc Res. 2021;117(13):2664–76.

    CAS  PubMed  Google Scholar 

  43. Wu L, et al. P2y12 Receptor promotes pressure overload-induced cardiac remodeling via platelet-driven inflammation in mice. Hypertension. 70(4):759–769.

  44. Schwinger RHG. Pathophysiology of heart failure. Cardiovascular diagnosis and therapy. 2021;11(1):263–76.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Adamo L, et al. Reappraising the role of inflammation in heart failure. Nat Rev Cardiol. 2020;17(5):269–85.

    Article  PubMed  Google Scholar 

  46. Adamo L, et al. Proteomic signatures of heart failure in relation to left ventricular ejection fraction. J Am Coll Cardiol. 2020;76(17):1982–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Latif N, et al. Frequency and specificity of antiheart antibodies in patients with dilated cardiomyopathy detected using SDS-PAGE and western blotting. J Am Coll Cardiol. 1993;22(5):1378–84.

    Article  CAS  PubMed  Google Scholar 

  48. Youker KA, et al. High proportion of patients with end-stage heart failure regardless of aetiology demonstrates anti-cardiac antibody deposition in failing myocardium: humoral activation, a potential contributor of disease progression. Eur Heart J. 2014;35(16):1061–8.

    Article  CAS  PubMed  Google Scholar 

  49. Keppner L, et al. Antibodies aggravate the development of ischemic heart failure. Am J Physiol Heart Circ Physiol. 2018;315(5):H1358-h1367.

    Article  PubMed  CAS  Google Scholar 

  50. Schulze K, et al. Antibodies to ADP-ATP carrier–an autoantigen in myocarditis and dilated cardiomyopathy–impair cardiac function. Circulation. 1990;81(3):959–69.

    Article  CAS  PubMed  Google Scholar 

  51. Hasham MG, et al. Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease. Dis Model Mech. 2017;10(3):259–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Okazaki T, et al. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med. 2003;9(12):1477–83.

    Article  CAS  PubMed  Google Scholar 

  53. Bockstahler M, et al. Heart-specific immune responses in an animal model of autoimmune-related myocarditis mitigated by an immunoproteasome inhibitor and genetic ablation. Circulation. 2020;141(23):1885–902.

    Article  CAS  PubMed  Google Scholar 

  54. Matsui S, et al. Peptides derived from cardiovascular G-protein-coupled receptors induce morphological cardiomyopathic changes in immunized rabbits. J Mol Cell Cardiol. 1997;29(2):641–55.

    Article  CAS  PubMed  Google Scholar 

  55. Herda LR, et al. Effects of immunoadsorption and subsequent immunoglobulin G substitution on cardiopulmonary exercise capacity in patients with dilated cardiomyopathy. Am Heart J. 2010;159(5):809–16.

    Article  CAS  PubMed  Google Scholar 

  56. Staudt A, et al. Role of immunoglobulin G3 subclass in dilated cardiomyopathy: results from protein A immunoadsorption. Am Heart J. 2005;150(4):729–36.

    Article  CAS  PubMed  Google Scholar 

  57. Staudt A, et al. Potential role of autoantibodies belonging to the immunoglobulin G-3 subclass in cardiac dysfunction among patients with dilated cardiomyopathy. Circulation. 2002;106(19):2448–53.

    Article  CAS  PubMed  Google Scholar 

  58. Limas CJ, Goldenberg IF, Limas C. Autoantibodies against beta-adrenoceptors in human idiopathic dilated cardiomyopathy. Circ Res. 1989;64(1):97–103.

    Article  CAS  PubMed  Google Scholar 

  59. Jahns R, et al. Autoantibodies activating human beta1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure. Circulation. 1999;99(5):649–54.

    Article  CAS  PubMed  Google Scholar 

  60. Chiale PA, et al. Differential profile and biochemical effects of antiautonomic membrane receptor antibodies in ventricular arrhythmias and sinus node dysfunction. Circulation. 2001;103(13):1765–71.

    Article  CAS  PubMed  Google Scholar 

  61. Störk S, et al. Stimulating autoantibodies directed against the cardiac beta1-adrenergic receptor predict increased mortality in idiopathic cardiomyopathy. Am Heart J. 2006;152(4):697–704.

    Article  PubMed  CAS  Google Scholar 

  62. Liu HR, et al. Relationship of myocardial remodeling to the genesis of serum autoantibodies to cardiac beta(1)-adrenoceptors and muscarinic type 2 acetylcholine receptors in rats. J Am Coll Cardiol. 2002;39(11):1866–73.

    Article  CAS  PubMed  Google Scholar 

  63. Christ T, et al. Autoantibodies against the beta1 adrenoceptor from patients with dilated cardiomyopathy prolong action potential duration and enhance contractility in isolated cardiomyocytes. J Mol Cell Cardiol. 2001;33(8):1515–25.

    Article  CAS  PubMed  Google Scholar 

  64. Iwata M, et al. Autoimmunity against the second extracellular loop of beta(1)-adrenergic receptors induces beta-adrenergic receptor desensitization and myocardial hypertrophy in vivo. Circ Res. 2001;88(6):578–86.

    Article  CAS  PubMed  Google Scholar 

  65. Jane-wit D, Altuntas CZ, Johnson JM, Yong S, Wickley PJ, Clark P, Wang Q, Popovic ZB, Penn MS, Damron DS, Perez DM. β1-Adrenergic receptor autoantibodies mediate dilated cardiomyopathy by agonistically inducing cardiomyocyte apoptosis. Circulation. 2007;116(4):399-410.

  66. Nagatomo Y, et al. A pilot study on the role of autoantibody targeting the beta1-adrenergic receptor in the response to beta-blocker therapy for congestive heart failure. J Card Fail. 2009;15(3):224–32.

    Article  CAS  PubMed  Google Scholar 

  67. Fu LX, et al. Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy. J Clin Invest. 1993;91(5):1964–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Stavrakis S, et al. Opposing cardiac effects of autoantibody activation of β-adrenergic and M2 muscarinic receptors in cardiac-related diseases. Int J Cardiol. 2011;148(3):331–6.

    Article  PubMed  Google Scholar 

  69. Leuschner F, et al. Absence of auto-antibodies against cardiac troponin I predicts improvement of left ventricular function after acute myocardial infarction. Eur Heart J. 2008;29(16):1949–55.

    Article  PubMed  CAS  Google Scholar 

  70. Haghikia A, et al. Evidence of autoantibodies against cardiac troponin I and sarcomeric myosin in peripartum cardiomyopathy. Basic Res Cardiol. 2015;110(6):60.

    Article  PubMed  Google Scholar 

  71. Alvarez FL, et al. Heart-specific autoantibodies induced by Coxsackievirus B3: identification of heart autoantigens. Clin Immunol Immunopathol. 1987;43(1):129–39.

    Article  CAS  PubMed  Google Scholar 

  72. Zhang Y, et al. Low level antibodies against alpha-tropomyosin are associated with increased risk of coronary heart disease. Front Pharmacol. 2020;11.

  73. Shmilovich H, et al. Autoantibodies to cardiac troponin I in patients with idiopathic dilated and ischemic cardiomyopathy. Int J Cardiol. 2007;117(2):198–203.

    Article  PubMed  Google Scholar 

  74. Landsberger M, et al. Potential role of antibodies against cardiac Kv channel-interacting protein 2 in dilated cardiomyopathy. Am Heart J. 2008;156(1):92-99.e2.

    Article  CAS  PubMed  Google Scholar 

  75. Baba A, Yoshikawa T, Ogawa S. Autoantibodies produced against sarcolemmal Na-K-ATPase: possible upstream targets of arrhythmias and sudden death in patients with dilated cardiomyopathy. J Am Coll Cardiol. 2002;40(6):1153–9.

    Article  CAS  PubMed  Google Scholar 

  76. Zhang M, et al. The role of natural IgM in myocardial ischemia-reperfusion injury. J Mol Cell Cardiol. 2006;41(1):62–7.

    Article  CAS  PubMed  Google Scholar 

  77. Zhang M, et al. Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury. Proc Natl Acad Sci U S A. 2004;101(11):3886–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Vogel CW. The role of complement in myocardial infarction reperfusion injury: an underappreciated therapeutic target. Front Cell Dev Biol. 2020;8:606407.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Investigators AA, et al. Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial. JAMA. 2007;297(1):43–51.

    Article  Google Scholar 

  80. Martel C, et al. Pexelizumab fails to inhibit assembly of the terminal complement complex in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Insight from a substudy of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial. Am Heart J. 2012;164(1):43–51.

  81. Ludwig RJ, et al. Mechanisms of autoantibody-induced pathology. Front Immunol. 2017;8:603.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Haudek SB, et al. Fc receptor engagement mediates differentiation of cardiac fibroblast precursor cells. Proc Natl Acad Sci U S A. 2008;105(29):10179–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Staudt A, et al. Fc(gamma) receptors IIa on cardiomyocytes and their potential functional relevance in dilated cardiomyopathy. J Am Coll Cardiol. 2007;49(16):1684–92.

    Article  CAS  PubMed  Google Scholar 

  84. Doing A, et al. B-cell function in chronic heart failure: antibody response to pneumococcal vaccine. J Card Fail. 2001;7(4):318–21.

    Article  CAS  PubMed  Google Scholar 

  85. Sun Y, et al. Splenic marginal zone B lymphocytes regulate cardiac remodeling after acute myocardial infarction in mice. J Am Coll Cardiol. 2022;79(7):632–47.

    Article  CAS  PubMed  Google Scholar 

  86. Mo F, et al. Are activated B cells involved in the process of myocardial fibrosis after acute myocardial infarction? An in vivo experiment. BMC Cardiovasc Disord. 2021;21(1):5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Hanna A, Frangogiannis NG. The role of the TGF-β superfamily in myocardial infarction. Front Cardiovasc Med. 2019;6.

  88. Li Y, et al. B cells increase myocardial inflammation by suppressing M2 macrophage polarization in Coxsackie virus B3-induced acute myocarditis. Inflammation. 2019;42(3):953–60.

    Article  CAS  PubMed  Google Scholar 

  89. Mena I, et al. The role of B lymphocytes in coxsackievirus B3 infection. Am J Pathol. 1999;155(4):1205–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Lu J, et al. The absence of B cells disrupts splenic and myocardial Treg homeostasis in coxsackievirus B3-induced myocarditis. Clin Exp Immunol. 2022.

  91. Yu M, et al. TNF-α-secreting B cells contribute to myocardial fibrosis in dilated cardiomyopathy. J Clin Immunol. 2013;33(5):1002–8.

    Article  CAS  PubMed  Google Scholar 

  92. Guo Y, et al. Increased circulating interleukin 10-secreting B cells in patients with dilated cardiomyopathy. Int J Clin Exp Pathol. 2015;8(7):8107–14.

    PubMed  PubMed Central  Google Scholar 

  93. Salzer U, et al. Susceptibility to infections and adaptive immunity in adults with heart failure. ESC Heart Fail. 2022;9(2):1195–205.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Jiao J, et al. Defective circulating regulatory B cells in patients with dilated cardiomyopathy. Cell Physiol Biochem. 2018;46(1):23–35.

    Article  CAS  PubMed  Google Scholar 

  95. Goodchild TT, et al. Bone marrow-derived B cells preserve ventricular function after acute myocardial infarction. JACC Cardiovasc Interv. 2009;2(10):1005–16.

    Article  PubMed  Google Scholar 

  96. Mahrholdt H, et al. Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation. 2006;114(15):1581–90.

    Article  PubMed  Google Scholar 

  97. Caforio ALP, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013;34(33):2636–48.

  98. Matsumoto Y, Park IK, Kohyama K. B-cell epitope spreading is a critical step for the switch from C-protein-induced myocarditis to dilated cardiomyopathy. Am J Pathol. 2007;170(1):43–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Powell AM, Black MM. Epitope spreading: protection from pathogens, but propagation of autoimmunity? Clin Exp Dermatol. 2001;26(5):427–33.

    Article  CAS  PubMed  Google Scholar 

  100. Kandolf R, et al. Mechanisms and consequences of enterovirus persistence in cardiac myocytes and cells of the immune system. Virus Res. 1999;62(2):149–58.

    Article  CAS  PubMed  Google Scholar 

  101. Tschöpe C, et al. Targeting CD20+ B-lymphocytes in inflammatory dilated cardiomyopathy with rituximab improves clinical course: a case series. Eur Heart J Case Rep. 2019;3(3).

  102. Jahns R, et al. Direct evidence for a beta 1-adrenergic receptor-directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy. J Clin Invest. 2004;113(10):1419–29.

  103. • Cordero-Reyes AM, et al. Full expression of cardiomyopathy is partly dependent on B‐cells: A pathway that involves cytokine activation, immunoglobulin deposition, and activation of apoptosis. J Am Heart Assoc. 2016;5(1):e002484. This study establishes a clear connection between B cells and myocardial hypertrophy/fibrosis and thus points to a potential role of B cells in the pathogenesis of HFpEF.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Kallikourdis M, et al. T cell costimulation blockade blunts pressure overload-induced heart failure. Nat Commun. 2017;8:14680.

    Article  PubMed  PubMed Central  Google Scholar 

  105. van den Hoogen P, et al. Increased circulating IgG levels, myocardial immune cells and IgG deposits support a role for an immune response in pre- and end-stage heart failure. J Cell Mol Med. 2019;23(11):7505–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Baniaamam M, et al. Clinical improvement of cardiac function in a patient with systemic lupus erythematosus and heart failure with preserved ejection fraction treated with belimumab. BMJ Case Rep. 2021;14(1).

  107. •• Lewis GA, et al. Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial. Nat Med. 2021;27(8):1477–82. This phase II trial showed that the immunomodulatory drug pirfenidone has beneficial effects in patients with HFpEF. Since murine data connects mechanistically the cardioprotective effects of pirfenidone to its B cell modulating properties, this study points at a potential role of B cells in human HFpEF.

    Article  CAS  PubMed  Google Scholar 

  108. Aimo A, et al. Pirfenidone is a cardioprotective drug: mechanisms of action and preclinical evidence. Pharmacol Res. 2020;155:104694.

    Article  CAS  PubMed  Google Scholar 

  109. Sanchez-Trujillo L, et al. Phase II clinical trial testing the safety of a humanised monoclonal antibody anti-CD20 in patients with heart failure with reduced ejection fraction, ICFEr-RITU2: study protocol. BMJ Open. 9(3):e022826.

  110. Zhao TX, et al. Rituximab in patients with acute ST-elevation myocardial infarction: an experimental medicine safety study. Cardiovasc Res. 2022;118(3):872–82.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Luigi Adamo is the recipient of NHLBI grants 5K08HLO145108-03 and 1R01HL160716-01.

Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Kevin Bermea, Aashik Bhalodia, Angelo Huff, Sylvie Rousseau & Luigi Adamo

Authors
  1. Kevin Bermea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aashik Bhalodia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Angelo Huff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sylvie Rousseau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luigi Adamo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luigi Adamo.

Ethics declarations

Conflict of Interest

Luigi Adamo is co-founder of i-Cordis, LLC, a start-up company focused on the development of immunomodulatory therapies for heart failure, with a special emphasis on B cells and pirfenidone derivatives. He reports a small reimbursement for 1-h consultation for Cello Health BioConsulting. He also has patents planned, issued, or pending for WO/2019/028062, WO2010121122 A3, WO2008021465 A8, and US20070249038 A1. The other authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of Topical Collection on Myocardial Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bermea, K., Bhalodia, A., Huff, A. et al. The Role of B Cells in Cardiomyopathy and Heart Failure. Curr Cardiol Rep 24, 935–946 (2022). https://doi.org/10.1007/s11886-022-01722-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11886-022-01722-4

Keywords

Search

Navigation