1 Cell autonomous pre-BCR signaling Onishi and Melchers Nature Immunology Sept 2003.

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Transcript of 1 Cell autonomous pre-BCR signaling Onishi and Melchers Nature Immunology Sept 2003.

  • Cell autonomous pre-BCR signaling

    Onishi and MelchersNature ImmunologySept 2003

  • Stadien der B-Zellreifung SptePro-B-ZelleSptePr-B-ZelleB-ZelleFrhe Pr-B-ZelleStamm-zelleFrhePro-B-Zelle

  • Immunoglobulin-RezeptorenmHIga/bmHIga/bPr-B-ZellrezeptorB-Zellrezeptor

  • Structure of associated VpreB and 5 protein as proposed by Kudo et al. (6), the Ig-like portions of VpreB (-strands 16 in red) and 5 (C5, -strands 17, amino terminal pair 7-strand in blue) are assumed to fold as Ig domains. The figure is modified from that published in ref. 6.

  • Initiierung von Pr-B-Zellrezeptorsignalen?? Konstitutiv vom ERKonstitutiv von der Zelloberflche nach SelbstligationStromazell-Liganden induziertER ER cytoplasm ? Ligand cytoplasm ER cytoplasm ? ? ER ?Konstitutiv von der Zelloberflche

  • Region to be deleted5 35 33 5 3 52 getrennte PCRs5 33 5`5 33 5`Mix, Anneal5 33 5`2. PCRDeletion durch overlap extension

  • Immunprzipitation von Oberflchen Pr-BZRX-Tyr-PRat anti-mousepreBCR (Fab)SL156Protein A-sepharoseMouse anti-rat kappa(MAR18.5)Pre-B line

  • Proliferative Signale whrend der Entwicklung frher B-lymphoider Zellen ProKM-StromazelleProProPrSCFc-kitIL7Pr-BZRIL7-RVCAM-1VLA-4Pr-BZR-Ligand???Proliferative Expansion und Differenzierung