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Cell autonomous pre-BCR signaling
Onishi and MelchersNature Immunology
Sept 2003
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Stadien der B-Zellreifung Stadien der B-Zellreifung
D JH VH DJH
Schwere Ig-Kette (H)
VL JL
Leichte Ig-Kette (L)
SpätePro-B-Zelle
SpätePrä-B-Zelle B-ZelleFrühe Prä-B-
Zelle
Stamm-zelle
FrühePro-B-Zelle
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Immunoglobulin-RezeptorenImmunoglobulin-Rezeptoren
H
Ig/
H
Ig/
VpreB
5
Prä-B-Zellrezeptor B-Zellrezeptor
IgL
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Structure of associated VpreB and λ5 protein as proposed by Kudo et al. (6), the Ig-like portions of VpreB (β-strands 1–6 in red) and λ5 (Cλ5, β-strands 1–7, amino terminal pair β7-strand in blue) are assumed to fold as Ig domains. The figure is modified from that published in ref. 6.
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Initiierung von Prä-B-Zellrezeptorsignalen?? Initiierung von Prä-B-Zellrezeptorsignalen??
Konstitutiv vom ER
Konstitutiv von der Zelloberfläche nach Selbstligation
Stromazell-Liganden induziert
ER ER
cytoplasm ?
Ligand
cytoplasm
ER
cytoplasm ?
?
ER
?
Konstitutiv von der
Zelloberfläche
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Region to be deleted5´ 3´5´
3´
3´
5´ 3´ 5´
2 getrennte PCRs5´ 3´
3´ 5`
5´ 3´
3´ 5`
Mix, Anneal5´ 3´
3´ 5`
2. PCR
Deletion durch overlap extension
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Immunpräzipitation von Oberflächen Prä-BZRImmunpräzipitation von Oberflächen Prä-BZR
X-Tyr-P
Rat anti-mousepreBCR (Fab)SL156
Protein A-sepharose
Mouse anti-rat kappa(MAR18.5)
Pre-B line
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Proliferative Signale während der Entwicklung Proliferative Signale während der Entwicklung früher B-lymphoider Zellen früher B-lymphoider Zellen
Pro
KM-Stromazelle
ProPro
PräSCFc-kit
IL7Prä-BZR
IL7-R
VCAM-1
VLA-4
Prä-BZR-Ligand???
Proliferative Expansion und Differenzierung