Involvement of CD72 in membranoproliferative glomerulonephritis induced by Plasmodium chabaudi AS infection in NC/Jic mice.

NC/Jic mice infected with the rodent malaria parasite Plasmodium chabaudi AS (P. chabaudi AS) develop membranoproliferative glomerulonephritis (MPGN), a Type III hypersensitivity reaction. MRL/MpJ-lpr/lpr (MRL/lpr) mice, a murine model of systemic lupus erythematosus, also develop nephropathy, which is classified as a Type III hypersensitivity reaction. This nephropathy in MRL/lpr mice involves cluster of differentiation 72 (CD72), a negative regulator of B cell activation. NC/Jic mice harbored the same Cd72c haplotype as MRL/lpr mice. This haplotype is characterized by a seven amino acid deletion and 13 amino acid substitutions in the C-type lectin-like domain (CTLD) encoded by exon 8. In the present study, we investigated the contribution of the Cd72c haplotype to the development of MPGN in NC/Jic mice. NC/Jic-Cd72 knock-in (NC-Cd72 KI) mice, in which exon 8 of NC/Jic mice was replaced with normal exon 8 derived from the Cd72b haplotype, developed MPGN to a degree comparable to that in NC/Jic mice. In contrast, NC/Jic mice lacking exon 8 of Cd72 (NC-Cd72 Δex8) exhibited significantly attenuated MPGN severity. These results suggest that exon 8 of Cd72 is involved in the development of malaria-induced MPGN in NC/Jic mice, whereas the Cd72c haplotype is not the primary cause.