Role of bone marrow cells in autoantibody production and lymphoproliferation in the novel mutant strain of mice, CBA/KlJms-lprcg/lprcg.
The novel mutant gene, lprcg, is allelic with lpr, but complements the gld gene in induction of lymphoproliferation. Mice with this autosomal recessive mutation, CBA/KlJms-lprcg/lprcg (CBA-lprcg), served in this study to analyze the abnormalities of bone marrow (BM) stem cells responsible for autoantibody production and lymphoproliferation by BM transfer experiments. Transferred CBA-lprcg BM cells might have differentiated into so-called double-negative, anomalous lymphoid cells and caused production of autoantibodies such as anti-DNA antibodies in the environment of normal CBA/KlJms-(+)/+ (CBA-(+)) mice. Macroscopic graft-vs.-host-like disease as reported in lpr----non-lpr BM transfer was not observed in these recipients. In this BM chimera, however, lymphoproliferation did not ensue and the host's lymph nodes became atrophic. The lymphoproliferation required the coexistence of lprcg BM cells and lprcg lymph nodes in CBA-(+) mice. The results indicate that the functions of the lprcg gene are expressed at both BM and lymph node levels. Thus, this mutant strain of mice should provide an excellent model for analyzing aberrant lymphocyte differentiation from the BM cells leading to autoimmunity and lymphoproliferative disorder.
Kimura
M
M
Department of Internal Medicine, University of Tokyo, Japan.
Katagiri
T
T
Kikuchi
Y
Y
Shimada
K
K
Nariuchi
H
H
Wakabayashi
T
T
Matsuzawa
A
A
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001323:Autoantibodies / Q000096:biosynthesis*; D001853:Bone Marrow / Q000473:pathology / Q000502:physiology*; D017493:Leukocyte Common Antigens; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D001323:Autoantibodies; D018800:Thy-1 Antigens; D017493:Leukocyte Common Antigens