Intracellular demonstration of active TGF beta 1 in B cells and plasma cells of autoimmune mice - IgG-Bound TGF beta 1 suppresses neutrophil function and host defense against Staphylococcus aureus infection

Infection remains a leading cause of morbidity and mortality in patients with SLE. To investigate this, previously we assessed the host defense status of autoimmune MRL/1pr mice and found that elaboration of active TGF beta suppressed neutrophil function and decreased survival in response to Staphylococcus aureus infection. The purpose of the present work was to elucidate the molecular form and the cellular source of the active TGF beta involved. Here, we report for the first time that TGF beta 1 is found in the active form inside B cells and plasma cells and that it circulates in the plasma complexed with IgG in two murine models of systemic autoimmunity and in some patients with SLE. IgG-bound active TGF beta 1 is many times more potent than uncomplexed active TGF beta 1 for suppression of neutrophil function in vitro and host defense against S. aureus infection in vivo. These data indicate that TGF beta 1 is in the active form inside B cells and plasma cells, that the formation of a complex of IgG and active TGF beta 1 is greatly accelerated in autoimmunity, and that this complex is extremely potent for suppression of PMN function and host defense against bacterial infection.