Phosphoinositide 3-kinase activation by Igbeta controls de novo formation of an antigen-processing compartment.
Antigens that bind B cell antigen receptor (BCR) are preferentially and rapidly processed for antigen presentation. The BCR is a multimeric complex containing a signaling module composed of Igalpha and Igbeta. Signaling pathways implicated in antigen presentation through the BCR are ill defined. Here we demonstrate that phosphoinositide 3-kinase (PI3K) inhibitors preclude antigen presentation induced by BCR or Igbeta but not Igalpha. Unraveling the mechanisms responsible for this inhibition, we show that PI3K inhibitors block neither antigen internalization nor degradation. Rather PI3K inhibitors block de novo formation of a multivesicular antigen processing compartment, which is induced by triggering of the BCR or Igbeta. Strikingly, we found using fluorescent probes binding specifically to PI3K products that BCR and Igbeta but not Igalpha induce PI3K activation in endocytic compartments wherein antigen is transported. Altogether, these results strongly suggest that Igbeta couples the BCR to PI3K activation that is instrumental for de novo formation of the antigen processing compartment and efficient antigen presentation.
Granboulan
Marie
M
INSERM U520, UMR 144, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
Lankar
Danielle
D
Raposo
Graça
G
Bonnerot
Christian
C
Hivroz
Claire
C
D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D007136:Immunoglobulins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D014407:Tumor Cells, Cultured
D000941:Antigens; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007136:Immunoglobulins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011947:Receptors, Antigen, B-Cell; C038767:immunoglobulin B