Lecture 7

Question 1

What is the default signalling pathway for B and T cell development?

Answer 1

apoptosis

Question 2

How are HSCs commited to the B cell lineage?

Answer 2

• HSC– MPP– CLP that expresses IL-7
• Kit/SCF binding + CXCL12 to retain in the bone marrow

Question 3

What transcription factors are expressed on the B cell once it has committed to the B cell lineage? What does this allow for?

Answer 3

E2A, EBF, Pax-5
- allows for cell to express genes needed to make BCR (RAG1/2, lambda5 and VpreB, Iga and Igb)

Question 4

What is the first checkpoint of B cell assembly?

Answer 4

• 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

Question 5

What makes the surrogate light chain?

Answer 5

lambda5 and VpreB: genes that don’t undergo rearrangement and code for the surrogate light chain

Question 6

What are some reasons that the B cell cannot make a function H chain polypeptide?

Answer 6

P/N nucleotides result in a stop codon, or H chain couldn’t properly pair with the surrogate light chain

Question 7

What happens after the pre-B cell receptor is made successfully?

Answer 7

• takes a break
• stops expressing RAG-1/2, TdT, lambda5 and VpreB

Question 8

What is the consequence of not expressing TdT after heavy chain is assembled?

Answer 8

TdT gets diluted out, no N nucleotides at the V-J joints

Question 9

What is light chain rescue?

Answer 9

When all of the options for rearrangement fail on the K light chain, the lambda chain starts recombination

Question 10

What is the second checkpoint in B cell development?

Answer 10

BCR is screened for self reactivity (its an immature B cell rn)

Question 11

Why does the light chain rearrangement have a greater chance of success?

Answer 11

• no N nucleotides
• isotopic exclusion on top of allelic exclusion

Question 12

Where does D to J rearrangement happen? Where does V to DJ rearrangement happen? (BCells)

Answer 12

D to J rearrangements occur on both chromosomes. V to DJ rearrangements
occur on one chromosome