Allotype-linked production of an idiotype-specific factor that promotes idiotype expression in nonresponder strains.

Abstract

We had previously demonstrated that expression of the cross-reactive idiotypes (CRI) in the phenyltrimethylammonium (TMA) system depends on the presence of a second-order T helper (Th2) cell. Furthermore, we showed that this cell type can be replaced by an idiotype-specific helper factor derived from either a 24-hr concanavalin A supernatant (Con A) or the T cell hybridoma LOP 1.4. This factor, regardless of its source, is idiotype-specific, I-J+, and promotes in vitro expression of the cross-reactive phenyltrimethylammonium idiotype (CRI+-TMA) found on anti-trinitrophenyl antibodies. Because the expression of this idiotype in antigen-primed immune sera is linked to the Ig-1e heavy chain locus, experiments were conducted to test whether the production of this factor was also linked to the same locus. Of the strains tested, only splenocytes derived from the Ig-1e mice, irrespective of their background genetics, produced the factor upon Con A stimulation. Furthermore, the function of the factor is not major histocompatibility complex (MHC)-restricted because Con A supernatants derived from the C57.Ige (H-2b, Ig-1e), NZB (H-2d, Ig-1e), and A.SW (H-2s, Ig-1e) strains promoted CRI+ trinitrophenyl plaque-forming cells in A/J (H-2a, Ig-1e) cultures. Further experiments were carried out to determine if the idiotype-specific factor could promote CRI+ TNP plaque-forming cells in non-Ig-1e strains. To this end, A/J Con A and LOP 1.4-derived supernatants were added to primed C57Bl/6 (H-2b, Ig-1b) and DBA/2 (H-2d, Ig-1c) splenic cultures, both of which do not express serum CRI-TMA or produce the idiotype-enhancing factor. The cultures from either strain in the presence of the factor produced CRI+-TMA trinitrophenyl plaque-forming cells of comparable numbers to the A/J prototype strain. The results suggest an important regulatory role for this factor in allotype-linked expression of dominant idiotypes.