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Bone marrow cell intrinsic defect drives autoimmunity in New Zealand Black chromosome 13 congenic mice
Author(s) -
Loh Christina M,
Pau Evelyn,
Chang NanHua,
Wither Joan E
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.667.14
Subject(s) - congenic , bone marrow , phenotype , biology , chromatin , autoimmunity , immunology , antibody , cell , immune system , systemic lupus erythematosus , microbiology and biotechnology , pathology , genetics , medicine , disease , gene
Introgression of a New Zealand Black (NZB) chromosome 13 interval onto a lupus‐resistant B6 background (denoted, c13) is sufficient to produce many of the hallmarks of lupus, including, high titre anti‐chromatin antibody (Ab) production, abnormal T cell activation, and renal disease. These phenotypes occurred in the presence of a dendritic cell (DC) expansion. In this follow‐up study, we sought to localize and characterize the immune defects leading to these pathogenic abnormalities; this was achieved by generating subcongenic mice and bone marrow (BM) reconstituted mice, respectively. Subcongenic mouse strains, c13(47–89 Mb), c13(73–114 Mb), and c13(81–114 Mb), all demonstrated low titre anti‐chromatin Ab production, abnormal T cell activation, and DC expansion. Lethally irradiated B6.Thy1aIgHa mice were reconstituted with BM cells from B6.Thy1aIgHa, c13, or a mixture of both. Only mice reconstituted with c13 BM cells developed the aforementioned phenotypes. Moreover, in mixed BM chimeras, these abnormalities were seen in both B6.Thy1aIgHa‐ and c13‐derived cells. Thus, this study shows that a BM cell‐intrinsic defect that is not cell‐autonomous is driving the c13 mouse phenotype. Furthermore, this defect can be localized within the overlapping 81–89 Mb subcongenic chromosome 13 interval. Source of research support: The Arthritis Society and Canadian Institutes of Health Research.