| 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
|
|
WOS Category
|
PATHOLOGY
|
| Resource |
| Mice |
RBRC01908 |
