Tolerance through Indifference: Autoreactive B Cells to the Nuclear Antigen La Show No Evidence of Tolerance in a Transgenic Model
| Autor: | Catherine L. Keech, Brett D. Aplin, Andrea de Kauwe, Tom P. Gordon, Dana Cavill, James McCluskey |
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| Rok vydání: | 2003 |
| Předmět: |
Lipopolysaccharides
Cell Survival T cell Immunology Naive B cell Antibody Affinity B-Lymphocyte Subsets Immunoglobulins Receptors Antigen B-Cell Bone Marrow Cells Mice Transgenic Human leukocyte antigen Biology Lymphocyte Activation Transfection Autoantigens Epitope Cell Line Immune tolerance Mice Antigen Antibody Specificity Immune Tolerance medicine Animals Humans Lupus Erythematosus Systemic Immunology and Allergy Cells Cultured B cell Autoantibodies Antibodies Monoclonal Receptor editing Cell Differentiation Cell biology Mice Inbred C57BL Sjogren's Syndrome medicine.anatomical_structure Immunoglobulin M Ribonucleoproteins Models Animal Spleen Signal Transduction |
| Zdroj: | Flinders University PURE Scopus-Elsevier |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Systemic autoimmune diseases are characterized by the production of high titer autoantibodies specific for ubiquitous nuclear self-Ags such as DNA, Sm, and La (SS-B), so the normal mechanisms of B cell tolerance to disease-associated nuclear Ags have been of great interest. Mechanisms of B cell tolerance include deletion, anergy, developmental arrest, receptor editing, and B cell differentiation to the B-1 subtype. However, recent studies in our laboratory have suggested that B cell tolerance to the nuclear autoantigen La is limited in normal mice, and tolerance may reside primarily in the T cell compartment. To test this hypothesis, we created Ig transgenic mice expressing the IgM H chain from an mAb specific for a xenogeneic epitope within human La (hLa). These mice were bred with hLa-transgenic mice that constitutively express hLa in a manner comparable to endogenous mouse La. Between 5–15% of transgenic B cells developing in the absence of hLa were specific for hLa, and these cells were neither depleted nor developmentally arrested in the presence of endogenous hLa expression. Instead, these autoreactive B cells matured normally and differentiated into Ab-forming cells, capable of secreting high titer autoantibody. Additionally, the life span of autoreactive hLa-specific B cells was not reduced, and they were phenotypically and functionally indistinguishable from naive nonautoreactive hLa-specific B cells developing in the absence of hLa. Together these data suggest a lack of intrinsic B cell tolerance involving any known mechanisms indicating that these autoreactive B cells are indifferent to their autoantigen. |
| Databáze: | OpenAIRE |
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