Resting small B cells present endogenous immunoglobulin variable-region determinants to idiotope-specific CD4+ T cells in vivo

Abstract

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 λ2 L-chain (Id+ mice). Another transgenic mouse strain expresses TCR transgenes with specificity for the Id (λ2)), 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-2b) 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.