Antigenic determinants localized within the highly diversified V-regions of Ig are called idiotopes (Id). Processed Id-peptides can be presented on MHC class II molecules to CD4(+) T cells. If B cells present their endogenous Id-peptides, T cell activation could occur in the absence of nominal antigen, a potentially important process in T-B cooperation and immune regulation. To test this idea, we used mice made transgenic for a lambda2 L-chain (Id(+) mice). Another transgenic mouse strain expresses TCR transgenes with specificity for the Id (lambda2), presented on MHC class II molecules. When highly purified sorted Id(+) B cells and Id-specific T cells were sequentially injected into MHC syngeneic SCID host, T cell became blastoid, CD69(+) and proliferated. To exclude any role of host APC, MHC incompatible Rag2(- / -) mice (H-2(b)) were used as recipients for the Id(+) B and Id-specific T cells, with similar results. Exposure to extracellular Id(+) immunoglobulin (Ig) was not sufficient for Id priming of B cells in vivo, highlighting the preferential presentation of Id peptides derived from endogenous Ig, by B cells. The results suggest that B cells presenting Id self-peptides generated by V(D)J recombinations or somatic mutations may directly stimulate T cell in vivo in the absence of conventional antigen.