Male BXSB mice develop a thymic hormonal dysfunction with presence of intraepithelial crystalline inclusions.
The thymus is morphologically abnormal in male BXSB mice with cortical involution densification of the epithelium and the presence of intraepithelial crystals. The thymic endocrine function in BXSB mice was appraised using a biological assay to measure the level of the zinc-dependent thymic hormone, thymulin, and an indirect immunofluorescence technique to evaluate the number of cells synthesizing the hormone within the thymus. Unlike the dramatically accelerated age-linked decline of thymulin production reported in females of other autoimmune strains (measured as early as 6 weeks of age), only male BXSB were affected, as compared to normal strains. The number of hormone-producing cells was significantly reduced in male BXSB thymuses, in parallel with this hormonal decrease. Thymulin inhibitory molecules were detected in male BXSB sera, as early as 8 weeks of age, as evaluated by their capacity to absorb in vitro and in vivo the biological activity of the hormone. These inhibitors are thymus dependent since they disappear after adult thymectomy. They are low MW molecules (less than 10 kDa), as previously found in normal aging mice, rather than autoantibodies, as evidenced in two autoimmune strains (B/W and db/db mice). These findings demonstrate that male BXSB mice develop thymic abnormalities very similar to those observed in other autoimmune strains. The presence of intrathymic crystals and of low MW inhibitors suggests the role of abnormal storage and the excretion of thymulin. This thymic dysfunction may play a role in the maintenance of B cell hyperactivity previously shown in BXSB males.
Dardenne
M
M
INSERM U 25, Hôpital Necker, Paris, France.
Savino
W
W
Nabarra
B
B
Bach
J F
JF
D000375:Aging; D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D004848:Epithelium / Q000276:immunology / Q000648:ultrastructure; D005260:Female; D005455:Fluorescent Antibody Technique; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000254:growth & development*; D008854:Microscopy, Electron; D012737:Sex Factors; D013935:Thymic Factor, Circulating / Q000032:analysis*; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology / Q000473:pathology*; D013951:Thymus Hormones / Q000032:analysis*
D001323:Autoantibodies; D013951:Thymus Hormones; D013935:Thymic Factor, Circulating