The healing myocardium mobilizes a distinct B-cell subset through a CXCL13-CXCR5-dependent mechanism

Cardiovasc Res. 2021 Nov 22;117(13):2664-2676. doi: 10.1093/cvr/cvab181.


Aims: Recent studies have revealed that B cells and antibodies can influence inflammation and remodelling following a myocardial infarction (MI) and culminating in heart failure-but the mechanisms underlying these observations remain elusive. We therefore conducted in mice a deep phenotyping of the post-MI B-cell responses in infarcted hearts and mediastinal lymph nodes, which drain the myocardium. Thereby, we sought to dissect the mechanisms controlling B-cell mobilization and activity in situ.

Methods and results: Histological, flow cytometry, and single-cell RNA-sequencing (scRNA-seq) analyses revealed a rapid accumulation of diverse B-cell subsets in infarcted murine hearts, paralleled by mild clonal expansion of germinal centre B cells in the mediastinal lymph nodes. The repertoire of cardiac B cells was largely polyclonal and showed no sign of antigen-driven clonal expansion. Instead, it included a distinct subset exclusively found in the heart, herein termed 'heart-associated B cells' (hB) that expressed high levels of Cd69 as an activation marker, C-C-chemokine receptor type 7 (Ccr7), CXC-chemokine receptor type 5 (Cxcr5), and transforming growth factor beta 1 (Tgfb1). This distinct signature was not shared with any other cell population in the healing myocardium. Moreover, we detected a myocardial gradient of CXC-motif chemokine ligand 13 (CXCL13, the ligand of CXCR5) on Days 1 and 5 post-MI. When compared with wild-type controls, mice treated with a neutralizing CXCL13-specific antibody as well as CXCR5-deficient mice showed reduced post-MI infiltration of B cells and reduced local Tgfb1 expression but no differences in contractile function nor myocardial morphology were observed between groups.

Conclusion: Our study reveals that polyclonal B cells showing no sign of antigen-specificity readily infiltrate the heart after MI via the CXCL13-CXCR5 axis and contribute to local TGF-ß1 production. The local B-cell responses are paralleled by mild antigen-driven germinal centre reactions in the mediastinal lymph nodes that might ultimately lead to the production of specific antibodies.

Keywords: B cells; Cardiac remodelling; Heart failure and immune cells; Myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism*
  • Cell Proliferation*
  • Chemokine CXCL13 / genetics
  • Chemokine CXCL13 / metabolism*
  • Chemokines / genetics
  • Chemokines / metabolism
  • Chemotaxis, Leukocyte*
  • Disease Models, Animal
  • Immunoglobulins / metabolism
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism*
  • Lymphocyte Activation*
  • Male
  • Mice, Inbred C57BL
  • Myocardial Infarction / genetics
  • Myocardial Infarction / immunology
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology
  • Myocardium / immunology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Phenotype
  • RNA-Seq
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / metabolism*
  • Signal Transduction
  • Single-Cell Analysis
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism


  • CXCR5 protein, mouse
  • Chemokine CXCL13
  • Chemokines
  • Cxcl13 protein, mouse
  • Immunoglobulins
  • Receptors, CXCR5
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1