Inherited hyperactivation of L-arginine synthesis in gamma + B lymphocytes of systemic autoimmune MRL mice.
The hyperactivation of B lymphocytes of MRL mice, which are an animal model for human systemic lupus erythematosus (SLE), is characterized as the preferential propagation of gamma + B lymphocytes and IgG overproduction followed by aging. Little is known about the molecular mechanisms, although the involvement of cytokines has been extensively investigated. Here we now show that gamma-committed B lymphocytes selectively exhibit a highly elevated L-citrulline metabolism while mu or alpha-committed B lymphocytes show a normal level in autoimmune MRL mice. L-Arginine proportionally supports the lymphocyte proliferation and antibody production in a concentration-dependent fashion (approximately 100 microM). However, normal murine lymphocytes show an extremely low activity of citrulline metabolism, which converts L-citrulline to L-arginine. Thus, these results suggest that the overexpression of elevated citrulline metabolism is associated with gamma chain expression, and this elevation may enable gamma-committed B lymphocytes to preferentially propagate and overproduce IgG compared with mu or alpha-committed B lymphocytes.
Sugimura
K
K
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Wada
Y
Y
Kimura
T
T
Ohno
T
T
Kobayashi
S
S
Azuma
I
I
D000818:Animals; D001120:Arginine / Q000096:biosynthesis* / Q000494:pharmacology; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002956:Citrulline / Q000494:pharmacology; D005260:Female; D007142:Immunoglobulin gamma-Chains / Q000378:metabolism; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D014508:Urea / Q000378:metabolism
D001323:Autoantibodies; D007142:Immunoglobulin gamma-Chains; D002956:Citrulline; D014508:Urea; D001120:Arginine