CELLULAR IMMUNOLOGY 84, 393-402 (1984) Strain Differences in the Development of Auto-anti-idiotypic Antibody Regulation with Age: Genetic Linkage to the Igh-C Locus’ MYRON R. SZEWCZUK’ Department of Microbiology and Immunology, Queen’s University, Kingston, Ontario K7L 3N6, Canada Received September 19, 1983; accepted November 23, I983 The effect of age on the appearance of anti-idiotype (Id)-blocked, hapten-augmentable plaque- forming cells (PFC) in various strains of mice was investigated. Strains of mice at 2 and 6-l 1 months of age were immunized with 500 pg trinitrophenylated bovine y-globulin (TNP-BGG) in complete Freund’s adjuvant (CFA) intraperitoneally. Splenic IgM and IgG anti-TNP PFC responses were assayed for anti-Id-blocked, hapten-augmentable PFC 14 days after immunization. It was found that strains differ with regard to the age at which they produce anti-Id-blocked, hapten-augmentable PFC. C57BL/6J (B6), DBA/l J, and C3H/HeJ mice produced a significantly high percentage of hapten-augmentable IgG anti-TNP PFC at 8-9 months of age as compared with the 2-month-old group. In contrast, 129/J, AKR/J, and C57L/J mice produced a signiticantly low percentage of hapten-augmentable PFC at 6-7 months of age as compared with the 2-month- old group. The CBA/J mice were high-hapten-augmentable plaque producers at both 2 and 7 months of age. SJL/J mice were, on the other hand, low producers at 2 and 11 months of age. Immune sera from high hapten-augmentable plaque-producing strains caused a hapten-reversible block of plaque formation by spleen cells from TNP-BGG-immune C57BL/6J mice and also revealed anti-(anti-TNP F(ab’)&G) titer as assayed by passive hemagglutination. This PFC- inhibiting activity in the immune sera of old C57BL/6J mice was an antibody of the IgC& and IgG, classes,lacked anti-TNP antibody activity, but reacted with anti-TNP antibody of C57BL/ 65 origin. Genetic analysis between high hapten-augmentable plaque production and allotypes in the (129/J X B6) crosses of the same H-2b haplotypes revealed that all of the backcrosses and F2 with high hapten-augmentable plaque production had the Igh-l8 allele of the high-producer, 129/J mouse. In contrast, the crosses with low hapten-augmentable plaque production were homozygous for the Igh- I b allele of the low-producer, B6 mouse. The data suggest strain differences in the development of auto-anti-idiotypic antibody regulation with age which may be controlled by a gene(s) linked to the Igh-C locus. INTRODUCTION Auto-anti-idiotypic antibodies have been shown to be responsible for a decline in the number of plaque-forming cells PFC,3 a reduction in the heterogeneity of avidity ’ This work was supported in part by grants-in-aid of research from the Muscular Dystrophy Association of Canada, Medical Research Council of Canada MA-7347, and Gerontology Research Council of Ontario. ’ Gerontology Research Council of Ontario Scholar. 3 Abbreviations used BGG, bovine y-globulin; CFA, complete Freund’s adjuvant; TNP, 2,4,6-trinitrophenyl group; TNP-BGG, trinitrophenylated bovine y-globulin; EACA, c-amino-n-caproic acid; PFC, plaque- forming cell(s); SRBC, sheep red blood cells; Hepes, N-2-hydroxyethylpiperazine-N’-2-ethanesulfonic acid; Id, idiotype (-ic). 393 0008-8749184 $3.00 Copyri&l Q 1984 by Academic Press. Inc. All rights of reproduction in any form reserved.