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Visualizing the onset and evolution of an autoantibody response in systemic autoimmunity.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2005 Jun 01; Vol. 174 (11), pp. 6872-8. - Publication Year :
- 2005
-
Abstract
- The onset of systemic autoimmunity is variable, making it difficult to identify early events. In this study, we show in rheumatoid factor (RF) Ig-transgenic autoimmune-prone mice that the appearance of RF B cells in blood signifies the onset of RF B cell activation in spleen, providing a novel window into the initiation of an autoantibody response. This allowed us to study the early and late phases of spontaneous induction of the B cell autoimmune response. Using this approach we showed that extensive Ab-forming cell generation in spleen, accompanied by somatic hypermutation, occurred despite the lack of an early germinal center response. The onset of the RF response correlated with the levels of IgG2a-containing immune complexes but not total IgG2a. By identifying the time of onset in individual mice, we were able to track progression of disease. We found remissions of RF Ab-forming cell production in some mice, suggesting that at the clonal level, chronic autoantibody responses are dynamic and episodic, much like acute pathogen responses. Surprisingly, there was little accumulation of long-lived plasma cells in bone marrow of mice with long-standing RF responses in spleen. These studies are among the first to define the early events of a spontaneous B cell autoimmune response.
- Subjects :
- Animals
Antibody-Producing Cells metabolism
Antibody-Producing Cells pathology
Antigen-Antibody Complex biosynthesis
Autoimmune Diseases genetics
Autoimmune Diseases pathology
B-Lymphocyte Subsets metabolism
B-Lymphocyte Subsets pathology
Disease Progression
Germinal Center cytology
Germinal Center immunology
Germinal Center metabolism
Immunoglobulin Allotypes biosynthesis
Immunoglobulin G biosynthesis
Immunoglobulin Light Chains biosynthesis
Immunoglobulin Variable Region biosynthesis
Kinetics
Lymphocyte Count
Mice
Mice, Inbred MRL lpr
Mice, Transgenic
Rheumatoid Factor blood
Rheumatoid Factor genetics
Spleen immunology
Spleen metabolism
Spleen pathology
Autoimmune Diseases immunology
B-Lymphocyte Subsets immunology
Evolution, Molecular
Rheumatoid Factor biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 174
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15905529
- Full Text :
- https://doi.org/10.4049/jimmunol.174.11.6872