Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental systemic lupus erythematosus can be induced in naive mice of different strains using a human monoclonal antibody bearing the 16/6 idiotype and a murine anti-16/6 Id monoclonal antibody designated 1A3-2. Herein we report the isolation of a second anti-16/6 Id antibody, 3F7-8, from BALB/c mice afflicted with experimental SLE. In contrast to the previously reported (1A3-2) anti-16/6 Id monoclonal antibody, mAb 3F7-8 does not induce experimental SLE upon immunization. The variable heavy and light chains of both antibodies were cloned and their sequences were determined. The VH of mAb 1A3-2 was found to express a germ line gene from the Q52 family, with a high homology to an anti-lysozyme antibody. The VH of monoclonal antibody 3F7-8 was found to express a 7183 germ line gene, showing over 95% homology with the VH of 12 anti-Sm antibodies isolated from MRL-lpr mice. Based on sequence homology to other known antibodies, we further demonstrated that monoclonal antibodies 1A3-2 and 3F7-8 bind lysozyme and the Sm ribonucleoproteins, respectively, in addition to their binding to the 16/6 Id.
Lupus 1996 Aug
PMID:Variable regions of two murine antibodies that bind the SLE associated 16/6 idiotype. 886 99

Lupus is characterized by a loss of B cell tolerance leading to autoantibody production. In this study, we explored the mechanisms underlying this loss of tolerance using B6 congenic mice with an interval from New Zealand Black chromosome 1 (denoted c1(96-100)) sufficient for anti-nuclear antibody production. Transgenes for soluble hen egg white lysozyme (sHEL) and anti-HEL immunoglobulin were crossed onto this background and various tolerance mechanisms examined. We found that c1(96-100) mice produced increased levels of IgM and IgG anti-HEL antibodies compared to B6 mice and had higher proportions of germinal center B cells and long-lived plasma cells, suggesting a germinal center-dependent breach of B cell anergy. Consistent with impaired anergy induction, c1(96-100) double transgenic B cells showed enhanced survival and CD86 upregulation. Hematopoietic chimeric sHEL mice with a mixture of B6 and c1(96-100) HEL transgenic B cells recapitulated these results, suggesting the presence of a B cell autonomous defect. Surprisingly, however, there was equivalent recruitment of B6 and c1(96-100) B cells into germinal centers and differentiation to splenic plasmablasts in these mice. In contrast, there were increased proportions of c1(96-100) T follicular helper cells and long-lived plasma cells as compared to their B6 counterparts, suggesting that both B and T cell defects are required to breach germinal center tolerance in this model. This possibility was further supported by experiments showing an enhanced breach of anergy in double transgenic mice with a longer chromosome 1 interval with additional T cell defects.
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PMID:Multiple tolerance defects contribute to the breach of B cell tolerance in New Zealand Black chromosome 1 congenic mice. 2862 73