RRC ID 31874
Author Aihara N, Kamiie J, Yamada M, Shirota K.
Title 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.
Journal Am J Pathol
Abstract 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 lymphoproliferation 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-1a 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-1a cells from infected mice showed that stimulation by C. hepatica soluble fraction promoted the proliferation of B-1a 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-1a cells is induced by co-stimulation by the specific pathogen antigen and IL-5 in the development of MC in C. hepatica-infected mice.
Volume 185(1)
Pages 172-84
Published 2015-1-1
DOI 10.1016/j.ajpath.2014.09.017
PII S0002-9440(14)00589-6
PMID 25452118
MeSH Animals Antigens, Helminth / immunology* B-Lymphocytes / cytology B-Lymphocytes / parasitology* Capillaria* Cell Proliferation Cryoglobulinemia / immunology Cryoglobulinemia / parasitology* Cryoglobulins / immunology Enoplida Infections / immunology* Eosinophils / cytology Female Immunoglobulin M / immunology Interleukin-5 / pharmacology* Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Microscopy, Fluorescence Phenotype Rheumatoid Factor / metabolism Spleen / cytology Spleen / parasitology* Th1 Cells / cytology Th2 Cells / cytology
IF 3.491
Times Cited 2
Mice RBRC01908