Autoantibodies to vascular smooth muscle are pathogenic for vasculitis. Am J Pathol 2005 Jun;166(6):1851-60
Date
05/28/2005Pubmed ID
15920169Pubmed Central ID
PMC1602413DOI
10.1016/S0002-9440(10)62494-7Scopus ID
2-s2.0-19544369142 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
We have previously shown that microvascular smooth muscle activates CD4+ T lymphocytes in sterile co-culture, presents antigen, and produces inflammatory cytokines. Adoptive transfer of lymphocytes co-cultured with syngeneic smooth muscle cells to healthy recipient mice results in vasculitic lesions predominantly in postcapillary venules. The present study assessed the pathogenic role of immunoglobulin and B cells in a murine model of vasculitis. Here, we show that transferred B cells, including plasmablast cells, accumulated, persisted, and proliferated in lung and secondary lymphoid organs of recipient mice. The induction of vasculitis was accompanied by production of IgM and IgG2a autoantibodies specific for vascular smooth muscle intracellular antigens. Circulating immunoglobulin had a pathogenic role in this vasculitis model, because the disease could be induced by transfer of serum from vasculitic mice to untreated animals but not by transfer of serum depleted of anti-smooth muscle autoantibodies. Additionally, the pathogenic mechanisms triggered by the transfer of vasculitogenic serum were dependent on T lymphocytes because both wild-type and B cell-deficient mice developed the disease after serum transfer, whereas RAG2-deficient mice did not. Thus, immunoglobulin and cell-mediated pathways work in concert to produce vasculitis in this model.
Author List
Baiu DC, Barger B, Sandor M, Fabry Z, Hart MNAuthor
Brittany Player DO Assistant Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adoptive TransferAnimals
Autoantibodies
B-Lymphocytes
Cell Proliferation
Cells, Cultured
Coculture Techniques
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Fluorescent Antibody Technique
Immunohistochemistry
Lymphocyte Activation
Male
Mice
Mice, Inbred BALB C
Muscle, Smooth, Vascular
Serum
T-Lymphocytes
Vasculitis
