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early Pro-B cell
rearrangement of D-J heavy chain genes
late Pro-B cell
rearrangement of VD-J heavy chain genes
large Pre-B cell
- VDJ heavy genes rearranged
- mu chain at surface of B cell w/ surrogate L chain
small Pre-B cell
rearrangement of V-J light chain genes
immature B cell
heavy and light chains come together on surface, quindi IgM now expressed on cell surface
mature B cell
IgD and IgM made from alternatively spliced H chain transcripts and are expressed on surface
What is the significance of mu heavy chain expression on cell surface?
signals cessation of heavy chain gene rearrangement and beginning of light chain gene rearrangement
What is a surrogate L chain?
made of VpreB and lambda 5 proteins assemble together to act as "L chain" on surface of large Pre-B cell with mu heavy chain
signals to stop mu chain rearrangement and begin L chain rearrangement
What happens when the small Pre-B cell becomes an immature B cell?
light chain gene rearrangement has been successful; now a full receptor expressed on outside; surrogate L chain no longer needed (VpreB and lambda 5 inhibited by completed real L chain)
How does RAG play a role in gene rearrangement?
stops expression of genes by phosphorylation in large Pre-B cell stage to stop rearranging but turns rearrangement back on for L chain rearrangement
How are immature B cells and negative selection related?
immature B cells are sensitive to negative selection in the bone marrow
What is negative selection?
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