Division of Molecular Immunology, Nikolaus-Fiebiger Center, FAU Erlangen-Nürnberg 1 Late Pro-B Late Pre-B Immature B cell Early Pre-B Stem cell Early Pro-B.

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Division of Molecular Immunology, Nikolaus-Fiebiger Center, FAU Erlangen-Nürnberg 1 Late Pro-B Late Pre-B Immature B cell Early Pre-B Stem cell Early Pro-B μHC fct ? LC ? Mature B cell Pairing of Ig chains 1 2 Autoreactivity 3 D→ JHD→ JH V H →DJ H V L → J L Checkpoints during B Cell Development

Division of Molecular Immunology, Nikolaus-Fiebiger Center, FAU Erlangen-Nürnberg 2 A B VλVλ JλJλ CλCλ VpreB λ5λ5 unique tails + H 3 N COO - + H 3 N COO λ LC 88 N-terminal part of 88 CDR1 CDR2 VpreB unique tails VLVL CDR1 CDR2 CDR3 Ig  /Ig  Cµ1Cµ1 Cµ2Cµ2 Cµ3Cµ3 Cµ4Cµ4 VHVH VpreB 5 µHC unique tails 88 + β8-UT of 5 C The Pre-B Cell Receptor Complex Vettermann et al., Sem. Immunol, 2006

Division of Molecular Immunology, Nikolaus-Fiebiger Center, FAU Erlangen-Nürnberg 3 Late Pro-B Late Pre-B Immature B cell Early Pre-B Stem cell Early Pro-B μHC fct ? LC ? Mature B cell Pairing of Ig chains 1 2 Autoreactivity 3 D→ JHD→ JH V H →DJ H V L → J L Checkpoints during B Cell Development

Division of Molecular Immunology, Nikolaus-Fiebiger Center, FAU Erlangen-Nürnberg 4 Control of pro-B and pre-B cell expansion Stroma cell E2F CDK4 D3 Rb E2F Cell cycle activators Rb P P P P P Pro-B cells IL7 D3 mRNA↑ ↑ Protein stability ↑ Stroma cell Pre- B cells Pre-BCR miRNA ? TF ? IL7 V H →D → J H Clarke Lab, Chicago Nature Immunollgy 2006

Division of Molecular Immunology, Nikolaus-Fiebiger Center, FAU Erlangen-Nürnberg 5 Why do we need SLC – Function 2? Ligand-independent pre-B cell autonomous Ligand-dependent pre-B cell autonomous Ligand-dependent stroma cell-dependent SC Ligand Signals induced by pre-BCR cross-linking Signals induced by pre-BCR assembly Ligand-independent pre-B cell autonomous Cross-linking and amplification of pre-BCR signals Ligand