Idiotype-specific CD4 super(+)CD25 super(+) T suppressor cells prevent, by limiting antibody diversity, the occurrence of anti-dextran antibodies crossreacting with histone H3

CD25 super(+) suppressor T cells regulate the immune response against the type-2 "thymus independent" bacterial polysaccharide antigen alpha (1 arrow right 3)dextran (Dex) in BALB/c mice. These T cells, represented by the clone 178-4 Ts, restrict the Dex-specific IgG antibody repertoire such that the J558 idiotype dominates. Antibodies with other structures in the heavy-chain variable region (V sub(H) region), predominantly within the CDR3 domain, occur when the T cell control fails. This increase of antibody diversity caused by a lack of CD25 super(+) Ts cells, e.g. in nude mice, does not result in the appearance of antibodies with enhanced affinity to the antigen Dex, but often leads to a crossreactivity with autologous proteins. Twenty-two out of sixty Dex-specific hybridomas from nude mice, but no hybridomas from euthymic mice, crossreact with a nuclear protein, as tested by ELISA. This nuclear protein was identified as histone H3. ten of the sixty hybridomas from nude mice were sequenced and show V sub(H) sequences that deviate from the original J558 sequence. Three of these ten hybridomas crossreact with the histone H3. Adoptive transfer of CD25 super(+) Ts cells to nude mice leads to a marked increase of antibodies carrying the original J558 idiotype within the IgG pool after immunization with Dex. Our data demonstrate a CD25 super(+) Ts cell-mediated restriction of V sub(H) usage, which prevents the appearance of crossreactive autoantibodies.