Lecture 7 Flashcards
What is the default signalling pathway for B and T cell development?
apoptosis
How are HSCs commited to the B cell lineage?
- HSC– MPP– CLP that expresses IL-7
- Kit/SCF binding + CXCL12 to retain in the bone marrow
What transcription factors are expressed on the B cell once it has committed to the B cell lineage? What does this allow for?
E2A, EBF, Pax-5
- allows for cell to express genes needed to make BCR (RAG1/2, lambda5 and VpreB, Iga and Igb)
What is the first checkpoint of B cell assembly?
- assembly of the pre-b cell receptor
- the heavy chain is checked with a surrogate light chain via cross linking -
- iga and igb are there to signal if the heavy chain works properly
What makes the surrogate light chain?
lambda5 and VpreB: genes that don’t undergo rearrangement and code for the surrogate light chain
What are some reasons that the B cell cannot make a function H chain polypeptide?
P/N nucleotides result in a stop codon, or H chain couldn’t properly pair with the surrogate light chain
What happens after the pre-B cell receptor is made successfully?
- takes a break
- stops expressing RAG-1/2, TdT, lambda5 and VpreB
What is the consequence of not expressing TdT after heavy chain is assembled?
TdT gets diluted out, no N nucleotides at the V-J joints
What is light chain rescue?
When all of the options for rearrangement fail on the K light chain, the lambda chain starts recombination
What is the second checkpoint in B cell development?
BCR is screened for self reactivity (its an immature B cell rn)
Why does the light chain rearrangement have a greater chance of success?
- no N nucleotides
- isotopic exclusion on top of allelic exclusion
Where does D to J rearrangement happen? Where does V to DJ rearrangement happen? (BCells)
D to J rearrangements occur on both chromosomes. V to DJ rearrangements
occur on one chromosome
