Autoimmune disease in Lyn-deficient mice is dependent on an inflammatory environment established by IL-6

Abstract

Lyn-deficient mice develop Ab-mediated autoimmune disease resembling systemic lupus erythematosus where hyperactive B cells are major contributors to pathology. In this study, we show that an inflammatory environment is established in Lyn-/- mice that perturbs several immune cell compartments and drives autoimmune disease. Lyn-/- leukocytes, notably B cells, are able to produce IL-6, which facilitates hyperactivation of B and T cells, enhanced myelopoiesis, splenomegaly, and, ultimately, generation of pathogenic autoreactive Abs. Lyn-/- dendritic cells show increased maturation, but this phenotype is independent of autoimmunity as it is reiterated in B cell-deficient Lyn-/- mice. Genetic del..