A genetic locus controlling aging-sensitive regression of B lymphopoiesis in an autoimmune-prone MRL/lpr strain of mice.
Aging readily affects immune system under the influence of environmental and/or intrinsic factors while accelerating the development of various immune disorders including autoimmune diseases. Little is known about molecular and cellular mechanisms connecting between immune senescence and development of autoimmune diseases. Here, we first show strain-specific and aging-sensitive onset of B-cell abnormality in a lupus-prone MRL/Mp.Fas(lpr) (MRL/lpr) strain of mice. This abnormality was characterized by the regression of B lymphopoiesis in the bone marrow of this strain. We next examined the association between the B-cell regression and onset of autoimmune diseases in aged (MRL/lpr x C3H/He.Fas(lpr)) F2 mice, in which pathologic phenotypes, such as glomerulonephritis, vasculitis, sialoadenitis and arthritis, variously developed. We also searched whole genome to identify genetic loci linked to the B-cell regression by using the same F2 mice. The B-cell regression manifested in the spleen of F2 mice was retrospectively evaluated by reverse transcriptase-based PCR quantification. The results demonstrated that the onset of autoimmune diseases in the F2 mice was not associated with the aging-sensitive B-cell regression. The genetic study identified a significant locus responsible for the B-cell regression in the vicinity of D5Mit233 (29 cM). This is first evidence for the presence of a genetic locus that affects B lymphopoiesis in an aging-sensitive manner.
Nakatani
K
K
First Department of Internal Medicine, Nara Medical University, Kashihara, Japan.
Qu
W-M
WM
Zhang
M-C
MC
Fujii
H
H
Furukawa
H
H
Miyazaki
T
T
Iwano
M
M
Saito
Y
Y
Nose
M
M
Ono
M
M
D000375:Aging / Q000235:genetics* / Q000276:immunology; D000483:Alleles; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000235:genetics; D001323:Autoantibodies / Q000097:blood / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr / Q000235:genetics*; D013047:Specific Pathogen-Free Organisms
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D005819:Genetic Markers