Strain differences in the development of auto-anti-idiotypic antibody regulation with age: Genetic linkage to the Igh-C locus

Abstract

The effect of age on the appearance of anti-idiotype (Id)-blocked, hapten-augmentable plaqueforming cells (PFC) in various strains of mice was investigated. Strains of mice at 2 and 6–11 months of age were immunized with 500 μg trinitrophenylated bovine γ-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/1J, 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 significantly 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′) 2-IgG) titer as assayed by passive hemagglutination. This PFC-inhibiting activity in the immune sera of old C57BL/6J mice was an antibody of the IgG 2a and IgG 3 classes, lacked anti-TNP antibody activity, but reacted with anti-TNP antibody of C57 BL 6 J origin. Genetic analysis between high hapten-augmentable plaque production and allotypes in the (129/J × 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-1 a allele of the high-producer, 129/J mouse. In contrast, the crosses with low hapten-augmentable plaque production were homozygous for the Igh-1 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.