Low-valency, but not monovalent, antigens trigger the B-cell antigen receptor (BCR).
Antigen binding to the B-cell antigen receptor (BCR) leads to receptor triggering and B-lymphocyte activation. Here, we have probed the molecular requirements for BCR triggering in primary murine B cells using a set of defined soluble haptenated peptides. Bi- and trivalent haptens activated the BCR, as measured by protein phosphorylation, Ca(2+) influx, BCR down-modulation and CD69, CD86 and MHC class II up-regulation. In contrast, four distinct monovalent haptens were ineffective. Next, we used two different anti-idiotypic antibodies, which bind to the antigen-combining site of the BCR. Again, monovalent Fab fragments were ineffective, whereas bivalent antibodies could stimulate the BCR. These findings are compatible with ligand-induced clustering of monomeric BCRs or re-organization of BCR complexes within pre-formed BCR oligomers. Lastly, an increase in the valency of the haptenated peptides improved the activation potential, whereas variations in the distance between two haptens had no effect. This finding contributes to understand how the immune system can efficiently recognize structurally diverse antigens but still discriminate between foreign and self.
Department of Molecular Immunology, Max-Planck-Institute of Immunobiology and Faculty of Biology, University of Freiburg, Stübeweg 51, 79108 Freiburg, Germany.
Susana
S
Minguet
Elaine-Pashupati
EP
Dopfer
Wolfgang W A
WW
Schamel
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000941:Antigens / Q000737:chemistry* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D055879:Gene Knock-In Techniques; D006241:Haptens / Q000737:chemistry / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D006241:Haptens; D011947:Receptors, Antigen, B-Cell