The Development of Mixed Cryoglobulinemia in Capillaria hepatica-Infected Mice Is Associated with the Capillaria Antigen-Induced Selective Proliferation of Splenic B-1a Cells in Response to Interleukin-5 Stimulation

摘要

Chronic infection by pathogens such as hepatitis C virus induces monoclonal or oligoclonal proliferation of B cells, which produce IgM rheumatoid factor, leading to the development of mixed cryogLobuLinemia (MC). Antigen-driven tymphoproliferation is essential to the onset of MC; however, the underlying mechanism is Largely unknown. Herein, we show that type II MC is induced by Capillaria hepatica infection through a mechanism in which splenic B-la cells reacting to C. hepatica-specific antigen selectively proliferate, producing IgM rheumatoid factor under co-stimulation of the specific worm antigen and IL-5. In vitro assays using B-la cells from infected mice showed that stimulation by C. hepatica soluble fraction promoted the proliferation of B-la cells and the secretion of IgM, which reacted with the 75-kDa antigen in the soluble fraction. The severity of MC was correlated with the increase in serum IL-5 Levels in the infected mice. Furthermore, i.p. injection of the soluble worm fraction caused MC without an inflammatory response in IL-5 transgenic mice, indicating that IL-5 is critical for the development of MC. These results indicate that the selective proliferation of IgM rheumatoid factor secreting B-la cells is induced by co-stimulation by the specific pathogen antigen and IL-5 in the development of MC in C. hepatica infected mice.