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

• Published in: European journal of immunology Vol. 29; no. 12; pp. 4043 - 4052
• Main Authors: Munthe, Ludvig Andre, Kyte, Jon Amund, Bogen, Bjarne
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH 01.12.1999
• Subjects: Animals; Antigen Presentation; Antigen‐presenting cell; B cell; B-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - immunology; Epitopes - immunology; Idiotope; Idiotype; Immunoglobulin Idiotypes; Immunoglobulin Variable Region - immunology; Lymphocyte Cooperation - immunology; Mice; Mice, Transgenic; Transgenic mouse
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/(SICI)1521-4141(199912)29:12<4043::AID-IMMU4043>3.0.CO;2-E

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.