B lymphocytes and systemic sclerosis

Abstract

Systemic sclerosis is characterized by fibrosis and autoimmunity. Systemic sclerosis displays a variety of abnormal immune activations, including the production of disease-specific autoantibodies, although the pathogenic relation between systemic autoimmunity and the clinical manifestations of systemic sclerosis remains unknown. Recent studies have rediscovered that B cells play critical roles in systemic autoimmunity and disease expression through various functions more than autoantibody production, such as antigen presentation and cytokine production. This review focuses on recent advances in understanding the B cell's role in systemic sclerosis. Patients with systemic sclerosis have altered B-cell homeostasis characterized by expanded naive B cells and diminished memory B cells. Although memory B cells are decreased in number, they are chronically activated, possibly because of CD19 over-expression in B cells from patients with systemic sclerosis. CD19 over-expression can be genetically explained in part by a polymorphism of CD19 promoter region. Similarly, B cells from a tight-skin mouse, a genetic model of systemic sclerosis, show augmented CD19 signaling and chronic hyper-reactivity. CD19 hyper-phosphorylation in tight-skin B cells is caused by impaired function of CD22, a negative response regulator expressed on B cells. Classic roles of autoantibody secretion may also be important in systemic sclerosis because autoantibodies to matrix metalloproteinases can be pathogenic in vivo. B cells may have more pathogenic roles in systemic sclerosis than had been appreciated. Further studies are required to clarify the precise molecular basis that links B cells and fibrosis. Collectively, B cells and B-cell-specific response regulators such as CD19/CD22 appear to be potential therapeutic targets of the disease.