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

CD25+ suppressor T cells regulate the immune response against the type-2 "thymus independent" bacterial polysaccharide antigen α(13)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 (VH region), predominantly within the CDR3 domain, occur when the T cell control fails. This increase of antibody diversity caused by a lack of CD25+ 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 VH sequences that deviate from the original J558 sequence. Three of these ten hybridomas crossreact with the histone H3. Adoptive transfer of CD25+ 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+ Ts cell-mediated restriction of VH usage, which prevents the appearance of crossreactive autoantibodies.