A novel function of B lymphocytes from normal mice to suppress autoimmunity in (NZB x NZW)F1 mice.
In systemic autoimmune-prone (NZB x NZW)F1 (NZB/W F1) mice, B-cell abnormalities characterized by hypergammaglobulinaemia accompanying autoantibodies have been thought to be a main cause of the disease. To examine a possible regulatory role of B cells in the disease manifestations, we injected, intravenously (i.v.), normal or autoimmune B cells into non-irradiated NZB/W F1 mice. The injection of splenic B cells from major histocompatibility (MHC)-matched or allogeneic normal mice caused a marked decrease in serum immunoglobulin G (IgG) levels of autoantibodies, delayed the appearance of proteinuria and prolonged life span, whereas treatment with splenic B cells from NZB/W F1 or X-linked immunodeficient (Xid) mice failed to suppress the autoimmunity. Moreover, in vitro polyclonal antibody responses to lipopolysaccharide (LPS) of NZB/W F1-derived B cells from the treated mice were markedly reduced. Interestingly, the treatment of NZB/W F1 mice at 16, 18 and 20 or at 20, 22 and 24 weeks of age was more effective than that at 6, 8 and 10 weeks. The treatment also inhibited the development of surface IgG+ (sIgG+) B cells and splenomegaly, prominent in aged NZB/W F1 mice. In addition, when untreated NZB/W F1 responding B cells were precultured with normal B cells in vitro for 3 days, they also diminished the autoantibody production to subsequent LPS stimulation. Hence, the present results imply a novel function of normal B cells to ameliorate autoimmune disease in NZB/W F1 mice by correcting their B-cell abnormalities, and indicate that NZB/W F1 and Xid mice possess defects in this regulatory B-cell function.
Ono
S
S
Division of Oncogenesis, Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka, Japan.
Shao
D
D
Yamada
S
S
Yang
Y
Y
Yamashita
M
M
Hamaoka
T
T
D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018929:Cell Culture Techniques; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000517:prevention & control*; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D013154:Spleen / Q000276:immunology
D007074:Immunoglobulin G; D008070:Lipopolysaccharides