[Studies on abnormal immune responses to thymus-dependent antigens in autoimmune MRL/MpJ-lpr/lpr mice]

Autoimmune MRL/MpJ-lpr/lpr (MRL-lpr/lpr) mice were analysed for antigen-specific immunocompetent cell activities in the in vitro secondary immune responses to a thymus-dependent antigen, DNP-KLH. Compared to age- and sex-matched lpr congenic MRL/MpJ-+/+ (MRL-+/+) mice, spleen cells from primed MRL-lpr/lpr mice even at the prelymphadenopathy stage produced 10-fold less IgG1 and IgG2a anti-DNP antibodies upon challenge in vitro with DNP-KLH. Co-culture experiments of primed immunocompetent cells from both mice were performed to determine which cell population or subset was defective. The KLH-specific helper activity of splenic T cells from primed MRL-lpr/lpr mice was markedly deficient at any age tested. Such defective helper activity was not due to the presence of suppressor T cells. Actually, no antigen-specific or -nonspecific suppressor T cell factor was extracted from primed MRL-lpr/lpr spleen cells. On the other hand, the secondary antibody-producing ability of splenic B (Lyb-5-B) cells from primed MRL-lpr/lpr mice was not impaired at younger age but progressively decreased with age. Limiting dilution analysis revealed that the frequency of KLH-specific helper T cells in KLH-primed spleen cells was 6 times lower in 3-month-old MRL-lpr/lpr than in MRL-+/+ mice. In contrast, the average amount of IgG1 anti-DNP antibodies per single helper T cell was similar in both MRL mice. These results suggest that the defective helper T cell activity in MRL-lpr/lpr mice is responsible for the marked deficiencies in secondary antibody productions, but such defect is not qualitative but quantitative. The possible explanations for the quantitative helper T cell defect in MRL-lpr/lpr mice with relation to previous works are discussed.