Immunoglobulin kappa light chain produced by cardiomyocytes and participates in maintaining intercalated disc integrity

Abstract It is widely accepted that immunoglobulins (Igs) are produced only by B cells and function as antibodies. However, growing evidence has proven that almost all non-B cells also produce Igs with nonconventional roles, such as promotion of cell survival, proliferation and migration. In this study, we identified Ig light chain (κ chain) expression in mouse and human cardiomyocytes, especially on intercalated discs (ICDs). Unexpectedly, conditional knockout (cKO) of Igκ in adult cardiomyocytes in mice resulted in significant hypotension, a rapid decrease in cardiac contractility and conduction defects. Histologically, Igκ knockout in mouse cardiomyocytes led to structural disruption of intercalated discs (ICDs) and loss of localization of adhesion-related N-cadherin and CX43 on ICDs. Mechanistic investigation indicated that Igκ can bind with plectin/desmoplakin, a complex that connects desmin and desmosomes and enhances the protein stability of plectin. In conclusion, Our findings identify Igκ expressed by cardiomyocytes as a new ICD-related molecule that participates in cardiomyocyte contraction and conduction by stabilizing plectin.