| Abstract | The role of B cells as antigen-presenting cells is being recognized increasingly in immune responses to infections and autoimmunity. We compared T cell responses in wild-type and B cell-deficient mice immunized with the thyrotrophin receptor (TSHR), the major autoantigen in Graves' disease. Three B cell-deficient mouse strains were studied: JHD (no B cells), mIgM (membrane-bound monoclonal IgM+ B cells) and (m + s)IgM (membrane-bound and secreted monoclonal IgM). Wild-type and B cell-deficient mice (BALB/c background) were studied 8 weeks after three injections of TSHR or control adenovirus. Only wild-type mice developed IgG class TSHR antibodies and hyperthyroidism. After challenge with TSHR antigen, splenocyte cultures were tested for cytokine production. Splenocytes from TSHR adenovirus injected wild-type and mIgM-mice, but not from JHD- or (m + s)IgM- mice, produced interferon (IFN)-gamma in response to TSHR protein. Concanavalin A and pokeweed mitogen induced comparable IFN-gamma secretion in all groups of mice except in the JHD strain in which responses were reduced. The absence in (m + s)IgM mice and presence in mIgM mice of an anamnestic response to TSHR antigen was unrelated to lymphoid cell types. Surprisingly, although TSHR-specific antibodies were undetectable, low levels of serum IgG were present in mIgM- but not (m + s)IgM mice. Moreover, IFN-gamma production by antigen-stimulated splenocytes correlated with IgG levels. In conclusion, T cell responses to TSHR antigen developed only in mice with IgG-secreting B cells. Consequently, in the TSHR-adenovirus model of Graves' disease, some normal B cells appear to be required for the development of memory T cells. |
| Authors | P Pichurin, H Aliesky, C-R Chen, Y Nagayama, B Rapoport, S M McLachlan
(Affiliation: Autoimmune Disease Unit, Cedars-Sinai Research Institute and School of Medicine, University of California, Los Angeles, USA.)
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| Journal | Clinical and experimental immunology
(Clin Exp Immunol)
Vol. 134
Issue 3
Pg. 396-402
(Dec 2003)
ISSN: 0009-9104 England |
| PMID | 14632743
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- Autoantibodies
- Immunoglobulin G
- Immunoglobulin M
- Receptors, Thyrotropin
- Thyroxine
|
| Topics |
- Adenoviridae
(genetics)
- Animals
- Autoantibodies
(blood)
- B-Lymphocytes
(immunology)
- Female
- Genetic Vectors
(administration & dosage)
- Graves Disease
(immunology)
- Immunoglobulin G
(blood)
- Immunoglobulin M
(blood)
- Immunologic Memory
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Mutant Strains
- Models, Animal
- Receptors, Thyrotropin
(genetics, immunology)
- T-Lymphocytes
(immunology)
- Thyroxine
(blood)
- Transduction, Genetic
(methods)
|
