Tetraparental mice reveal complex cellular interactions of the mutant, autoimmunity-inducing lpr gene.
Lpr is a murine recessive autosomal mutant gene that, in conjunction with the background genes of different inbred mouse strains, produces varied syndromes of lymphadenopathy and autoantibody production. We have investigated the cellular basis of the lpr determined phenomena by constructing allophenic (tetraparental) chimeras of MRL/Mp-lpr/lpr combined with C57BL/6 and MRL/+ combined with C57BL/6-lpr/lpr. The appearance of lymphadenopathy, lpr atypical T cells, and autoantibodies was found to depend on the relative amounts +/+ and lpr tissue. The failure of these three abnormalities to correlate in certain animals suggested different pathways of lpr gene action. Furthermore, in the lpr predominant animals, both the lymphadenopathy and autoantibodies were essentially entirely contributed by the lpr donor. The expression of the lpr gene within the same cells expressing the MRL or B6 background determined the pathologic and serologic manifestations characteristic of the disease of that lpr strain, despite the presence of +/+ cells of the other background in the same individual. The lpr syndrome thus depends on the intracellular interaction of the lpr and background genes, and on positive signalling between different lpr cell populations.
Katagiri
T
T
Department of Immunology, University of Tokyo, Japan.
Azuma
S
S
Toyoda
Y
Y
Mori
S
S
Kano
K
K
Cohen
P L
PL
Eisenberg
R A
RA
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics* / Q000473:pathology; D002678:Chimera; D005796:Genes; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation
D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M