Idiotype regulation: evidence for the involvement of Igh‐C‐restricted T cells in the M‐460 idiotype suppressive pathway

Abstract

Allotypic restriction of idiotype suppression has been shown in several idiotypic systems. It has also been demonstrated that naive BALB/c mice contain naturally occurring suppressor T cells capable of inhibiting the M‐460 idiotype expressed on BALB/c B cells, and that T cells from allotype‐congenic mice have no effect on this expression. Since we have previously shown that upon polyclonal activation B cells of all mice tested are capable of secreting M‐460‐positive anti‐2,4,6‐trinitrophenyl (TNP) antibodies, we postulated that idiotype suppressor cells may recognize idiotypes in conjugation with products of the Igh loci. In the present study we tested this hypothesis. The data clearly showed that regardless of their allotypic haplotype all strains of mice do possess suppressor cells capable of recognizing the M‐460 idiotype. However, mixing experiments indicated that the functional potential of these suppressor cells can only be expressed when T and B lymphocytes come from allotype‐matched animals. Efficient suppression in those cultures containing allotype‐matched but incompatible B and T cells at the I‐J region of the H‐2 locus could be detected. Finally, using allotypic recombinant strains of mice, we found evidence that the restrictive elements in idiotypic suppression are the product of genes mapping in the Igh‐C locus, or closely linked to it.