Memory to self-antigens in Systemic Lupus Erythematosus (P4020)

Abstract

Abstract Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease associated with auto-IgG antibodies, which are produced due to defective clearance of apoptotic cells (AC) and loss of tolerance to self-antigens. SLE follows flare and remission courses; disease symptoms can come rapidly and unpredictably, suggesting the presence of immune memory to self-antigens in patients. However, experimental evidence and molecular mechanisms behind this are not known. We set up a mouse model by injecting normal mice with syngenic AC weekly for 4 weeks that breaks tolerance and induces auto-IgG production. One month later the serum auto-IgG drops to pre-immune level, these mice can rapidly respond to a single AC injection and produce increased auto-IgGs. This memory-like response is transferable into naïve mice. Serum level of auto-IgG subclass IgG2, but not IgG1, is dramatically increased in the memory response compared to that in the primary response, which contribute to pathogenic effects. The memory auto-IgGs are produced via both germinal center and plasmablast pathways. Spectratyping shows that B-cell repertoire is more skewed in memory response than that in pre-immune and primary response. These observations demonstrate an inducible immune memory to self-antigen in normal mice and establish a model for study of SLE flare-like response in mice. In addition, this study suggests that the formation of immune memory to self-antigens contributes to the disease relapse in SLE patients.