Inherited hyperactivation of L-arginine synthesis in γ+B lymphocytes of systemic autoimmune MRL mice

Abstract

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.