@article{10.1172/jci.insight.120137, author = {Luigi Adamo AND Lora J. Staloch AND Cibele Rocha-Resende AND Scot J. Matkovich AND Wenlong Jiang AND Geetika Bajpai AND Carla J. Weinheimer AND Attila Kovacs AND Joel D. Schilling AND Philip M. Barger AND Deepta Bhattacharya AND Douglas L. Mann}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Modulation of subsets of cardiac B lymphocytes improves cardiac function after acute injury}, year = {2018}, month = {6}, volume = {3}, url = {https://insight.jci.org/articles/view/120137}, abstract = {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.}, number = {11}, doi = {10.1172/jci.insight.120137}, url = {https://doi.org/10.1172/jci.insight.120137}, }