DIFFERENTIAL PATHOGENESIS OF LETHAL MOUSEPOX IN CONGENIC DBA 2 MICE IMPLICATES NATURAL-KILLER-CELL RECEPTOR-NKR-P1 IN NECROTIZING HEPATITISAND THE 5TH-COMPONENT OF COMPLEMENT IN RECRUITMENT OF CIRCULATING LEUKOCYTES TO SPLEEN/

Innate resistance of C57BL/6 (B6) mice to lethal mousepox is controlle d by multiple genes. Previously, four resistance genes were localized to specific subchromosomal regions and transferred onto a susceptible DBA/2 (D2) background by serial backcrossing and intercrossing to prod uce congenic strains. Intraperitoneally inoculated ectromelia virus wa s uniformly lethal and achieved similar titers in BG and D2 mice but e licited differential responses in liver, spleen, and circulating blood leukocytes. The distribution of these response phenotypes in congenic strains linked control of phenotypes with specific subchromosomal reg ions. D2.R1 mice, which carried a differential segment of chromosome 6 , exhibited a BG liver response and intermediate spleen and circulatin g leukocyte responses, D2.R2 and D2.R4 mice, which carried differentia l segments of chromosomes 2 and 1, respectively, exhibited a D2 liver response, a B6 spleen response, and an intermediate circulating leukoc yte response, The localization of control of liver response phenotypes to chromosome 6 implicates cells that express natural killer (NK) cel l receptor NKR-P1 alloantigens. The localization of control of spleen and circulating leukocyte responses to chromosomes 1, 2, and G implica tes NK cells, the fifth component of complement, and a gene near the s electin gene complex in recruitment of circulating leukocytes to splee n.