Study of specific plasmablasts and plasma cells to lipidic particles in the mouse models of lupus generated by liposomes bearing lipidic particles stabilized with different inducers

Abstract

Systemic lupus erythematosus (SLE) is an inflammatory, multisystem, chronic an autoimmune disease of unknown etiology. In our research group, we developed a mouse model of lupus by the administration of liposomes bearing lipid particles stabilized by chlorpromazine, promazine or manganese in BALB/c mice. In this model, we have detected IgG antibodies against lipid particles, so we are studying the immune mechanisms of how IgG antibodies are generated against a lipid antigen. It is noteworthy that the production mechanisms of anti-lipid IgG antibodies are practically unknown and have not been studied in autoimmune diseases such as SLE. In previous works, we showed that B cells mainly respond through germinal center to generate IgG antibodies against lipid particles. Moreover, against protein antigens after germinal center reaction, B cells differentiate into secondary lymphoid organs to plasmablasts that are maintained in cell cycle, can be divided and are in circulation. Eventually these plasmablasts can differentiate into plasma cells that are no longer in the cell cycle and are set in a niche (mainly in bone marrow or less in secondary lymphoid organs) where they begin to secrete antibodies. In this work, we propose to study the mechanisms of plasmablasts and plasma cells, specific to a lipid antigen, that leads to the production of IgG antibodies. This is very important because the IgG autoantibodies are the main causes of autoimmunity and particularly the anti-lipid particles antibodies, which have been found in patients with SLE, leprosy and preeclampsia, are those that trigger the lupus like disease in the mouse.