Resting small B cells present endogenous immunoglobulin variable-region determinants to idiotope-specific CD4(+) T cells in vivo.
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.
Munthe
L A
LA
Institut of Immunology, University of Oslo, National Hospital, Oslo, Norway. l.a.munthe@ioks.uio.no
Kyte
J A
JA
Bogen
B
B
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic
D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region