Thymic epithelial cell abnormalities in (NZB x H-2u)F1 mice.
Thymic maturation processes including MHC restriction and self-recognition require intimate association of thymocytes and stromal cells. Compared to the thymic architecture of various "normal" control strains of mice, defects in the thymic microenvironment have been demonstrated in New Zealand black (NZB) mice. Moreover, it is well known that NZB(H-dd) mice, when crossed with NZW(H-2u) mice, (NZB x NZW)F1, display a unique spectrum of autoimmune disease manifestations, including murine SLE. Using an extensive panel of monoclonal antibodies that define the thymic microenvironment, we examined two additional strains of (NZB x H-2u)F1 mice: (NZB x C57BL/10.PL)F1 and (NZB x PL/J)F1 mice to investigate the contributions of the H-2 and non-H-2 loci to the thymic abnormalities previously documented to occur in murine lupus. NZB, NZW, and (NZB x NZW)F1 mice were studied concurrently as were two additional control strains C57BL/6 and C57BL/10Sn. NZW mice had a normal thymic architecture as did the other H-2u mice and the control strains. In contrast, (NZB x NZW)F1 mice had a significantly altered thymic microenvironment; mild thymic abnormalities were also found in (NZB x PL/J)F1 but not in (NZB x C57BL/10.PL)F1. As expected, (NZB x NZW)F1 mice developed elevated titers of autoantibodies to DNA, proteinuria, and decreased life span. Interestingly, only (NZB x PL/J)F1 mice had increased levels of IgM antibodies to dsDNA, but did not manifest IgG anti-DNA or reduced survival. Defects in thymic stromal cells are associated directly to autoimmunity and their origin appears to be determined by non-H-2 loci.
Takeoka
Y
Y
Division of Rheumatology, Allergy, and Clinical Immunology, University of California, School of Medicine, Davis 95616, USA.
Whitmer
K J
KJ
Chen
S Y
SY
Ansari
A A
AA
Boyd
R L
RL
Shultz
L D
LD
Suehiro
S
S
Gershwin
M E
ME
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000276:immunology; D001327:Autoimmune Diseases / Q000401:mortality; D004247:DNA / Q000276:immunology; D004848:Epithelium / Q000002:abnormalities / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology; D008206:Lymphatic Diseases / Q000276:immunology / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D011507:Proteinuria / Q000652:urine; D013950:Thymus Gland / Q000002:abnormalities* / Q000276:immunology / Q000473:pathology*
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D004247:DNA