Modulation of subsets of cardiac B lymphocytes improves cardiac function after acute injury

Luigi Adamo, Lora J. Staloch, Cibele Rocha-Resende, Scot J. Matkovich, Wenlong Jiang, Geetika Bajpai, Carla J. Weinheimer, Attila Kovacs, Joel D. Schilling, Philip M. Barger, Deepta Bhattacharya, Douglas L. Mann

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Despite the long-standing recognition that the immune response to acute myocardial injury contributes to adverse left ventricular (LV) remodeling, it has not been possible to effectively target this clinically. Using 2 different in vivo models of acute myocardial injury, we show that pirfenidone confers beneficial effects in the murine heart through an unexpected mechanism that depends on cardiac B lymphocytes. Naive hearts contained a large population of CD19+CD11b-CD23-CD21-IgD+IgMlo lymphocytes, and 2 smaller populations of CD19+CD11b+ B1a and B1b cells. In response to tissue injury, there was an increase in neutrophils, monocytes, macrophages, as well as an increase in CD19+ CD11b- B lymphocytes. Treatment with pirfenidone had no effect on the number of neutrophils, monocytes, or macrophages, but decreased CD19+CD11b- lymphocytes. B cell depletion abrogated the beneficial effects of pirfenidone. In vitro studies demonstrated that stimulation with lipopolysaccharide and extracts from necrotic cells activated CD19+ lymphocytes through a TIRAP-dependent pathway. Treatment with pirfenidone attenuated this activation of B cells. These findings reveal a previously unappreciated complexity of myocardial B lymphocytes within the inflammatory infiltrate triggered by cardiac injury and suggest that pirfenidone exerts beneficial effects in the heart through a unique mechanism that involves modulation of cardiac B lymphocytes.

Original languageEnglish
JournalJCI Insight
Issue number11
StatePublished - Jun 7 2018


  • B cells
  • Cardiology
  • Heart failure


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