Antigen-specific responses and ANA production in B6.Sle1b mice: A role for SAP |
| |
| Institution: | 1. Department of Clinical Immunology and Allergy, St. Anne''s Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic;2. CLIP — Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, 2nd Medical Faculty, Charles University Prague, University Hospital Motol, Prague, Czech Republic;3. Centre for Rheumatology Research, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK;1. Department of Dentistry, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Bldg., London, ON, Canada, N6A 5C1;2. Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Bldg., London, ON, Canada, N6A 5C1;3. Department of Ophthalmology, Lawson Health Research Institute, 268 Grosvenor Street, London, Ontario, Canada, N6A 4V2;4. Department of Pathology, Lawson Health Research Institute, 268 Grosvenor Street, London, Ontario, Canada, N6A 4V2;1. Division of Rheumatology and Clinical Immunology, Laboratory of Autoimmunity and Metabolism, Humanitas Research Hospital, Rozzano, Milan, Italy;2. Department of Clinical Nursing, University of Occupational and Environmental Health, Kitakyushu, Japan;3. BIOMETRA Department, University of Milan, Italy |
| |
| Abstract: | B6.Sle1b mice, which contain the Sle1b gene interval derived from lupus prone NZM2410 mice on a C57BL/6 background, present with gender-biased, highly penetrant anti-nuclear antibody (ANA) production. To obtain some insight into the possible induction mechanism of autoantibodies in these mice we compared antigen-specific T dependent (TD) and T independent (TI-II) responses between B6.Sle1b and B6 mice before the development of high ANA titers. Our results show that B6.Sle1b mice mount enhanced responses to a TI-II antigen. Additionally, the memory T cell response generated by a TD antigen also increased. This enhancement correlates with the greater ability of B cells from B6.Sle1b mice to present antigen to T cells. The SLAM Associated Protein (SAP) is critical for signaling of many of the molecules encoded by the SLAM/CD2 gene cluster, candidates for mediating the Sle1b phenotype; therefore, we also investigated the effect of sap deletion in these strains on the TD and TI-II responses as well as on ANA production. The results of these studies of responses to non-self-antigens provide further insight into the mechanism by which responses to self-antigens might be initiated in the context of specific genetic alterations. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
