Intrinsic B cell defect results in abnormal TD antigen response in lupus-prone mice (130.17)

Abstract

Abstract The response to TD antigen NP-KLH was compared between the lupus-prone B6.Sle1.Sle2.Sle3 (TC) mice and control B6 mice. The amount of anti-NP IgG Abs in TC mice was significantly decreased as compared to B6 mice. In contrast, total anti-IgG Abs and anti-dsDNA Abs were increased compared to B6 mice, indicating that the decreased was specific for the immunization. This corresponds to the known poor immunization response of lupus patients. In addition, germinal center (GC) NP-specific B cells were decreased in TC mice compared to B6 mice, although there was no difference in the total number of GC B cells between the two strains. Co-transfer of purified CD43- B and CD4+ T cells from either B6 or TC mice showed that a TC intrinsic B cell defect was involved. B6.Rag−/− mice transferred with non-T BM cells from immunized TC mice lost anti-NP antibody production unlike transfer with BM cells from B6 mice. In contrast, there was similar Ab production between the two strains when transferred with non-T splenocytes, indicating that long-lived plasma cells in TC mice accumulated in spleen, instead of migrating to BM. In conclusion, lupus-prone mice show a deficient response to NP-KLH, in which NP-specific B cells differentiate differently from autoantigen-specific B cells. This deficiency is due at least in part to a defect in B cell maturation and plasma cell migration. SLE susceptibility loci involved in these defects will be mapped in future.