Quiz 5 part 2 Flashcards
when is the rearrangement of heavy chain gene segments happening
in early pro-B and late pro-B
is it likely that heavy chain rearrangement will succeed or fail?
EXPLAIN
there is a high probability that it will fail.
junctional diversity (P and N nucleotides) can shift the reading frame of the nucleotide sequence, resulting in a non multiple of 3 and nonfunctional genes
explain why junctional diversity (P&N nucleotides) is both good and bad
good – it can generate a lot of diversity
bad — high probability of a frameshift mutation and ultimate failure
what is the probability of Pro-B cell rearrangements failing/succeeding
66% chance of NONproductive rearrangements
33% chance of productive rearrangements and development proceeding
between early pro-B and late pro-B, which has a better chance of a productive rearrangement?
EXPLAIN
early pro-B has a better chance at productive rearrangement
this is so because early pro-B is DJ recombination and D gene segments are functional in all 3 reading frames
the variable region only has ONE reading frame for the V-DJ recombination, so it’s less likely to be productive (1/3 chance)
explain how chromosomes play a role in heavy chain recombination
in early pro-b, since there’s a high chance of development, recombination happens on BOTH loci (chromosomes)
however, in late pro-b, recombination happens at 1 locus at a time. if rearrangement is not productive on one chromosome, we move to another and try again
if heavy chain rearrangement is successful, what happens?
the B cell differentiates into LARGE, dividing B cells, producing mu heavy chain
approximately what% of large pre B cells produce a functional mu heavy chain?
what happens if unsuccessful?
~50%
apoptosis
what is the checkpoint for late pro-B cells
testing to see if produced mu heavy chain is functional (productive)
tested if it’s able to associate with light chain
HOW is this checkpoint of the mu heavy chain conducted?
cells produce a SURROGATE light chain
VpreB — similar to variable region of light chain
lambda5 — similar to constant region of light chain
mu chain homodimers assemble with surrogate light chain, Iga and IgB IN THE ER
explain what the pre-B cell receptor is
the pre-B cell receptor IS THE CHECKPOINT PROCESS to test the mu heavy chain
mu heavy chain homodimers assemble with surrogate light chain, and coreceptors Iga and IgB IN THE ER
If the first checkpoint is passed, (the newly made mu functional chain CAN FORM A large pre B cell receptor)
WHAT HAPPENS
Iga and IgB have cytoplasmic tails that signals to the pro-b cell to:
-terminate gene rearrangements. no longer needed
-stimulate several rounds of cell division
-VpreB and lambda5 promote pre b cell receptor oligomerization
if the first checkpoint is NOT passed, what happens?
Iga and Igb do NOT give survival signals and the cell undergoes apoptosis
upon successful passing of the first checkpoint, several important signals are sent via transcription factors to stop further recombination.
explain this further
RAG complex proteins are ceased to be expressed
Degradation of existing RAG complex proteins
chromatin structure is remodeled, INHIBITING transcription
what is the purpose of these important signals, sent via transcription factors, to STOP FURTHER RECOMBINATION?
ALLELIC EXCLUSION
– no heavy chain rearrangement on the second locus
if both loci were allowed to produce heavy chains, B cell receptor binding would be suboptimal (low avidity)
allelic exclusion gives _______ B cell receptors with high avidity binding
HOMOGENEOUS
NO allelic exclusion gives ____ B cell receptors with low avidity binding
heterogeneous
structurally, what exactly are large pre-B cells?
large oligomers of repeating preBCRs
what happens to large pre-B cells?
they divide, producing ~100 clones of small pre-B cells.
this is called CLONAL EXPANSION
the large pre-B cells divide, producing ~100 clones of small pre-B cells (clonal expansion)
are all of these small pre-B cells producing the same heavy chain?
YES – -we turned everything off to prevent transcription of another heavy chain
do small pre-B cells still express the surrogate light chain?
NO – it was just a test
WHERE are small pre-B cells producing their heavy chain?
in the ER – the heavy chains are ready to assemble
is the small pre-b cell still expressing preBCR?
NO
in small pre-B cells, the rearrangement of _____ begins
light chain (VJ) rearrangement
in order for small pre-B cells to do light chain rearrangement, what has to happen?
RAG complex proteins must be reactivated
small pre-B cells are ______ of ______ with identical ________
small pre-B cells are HUNDREDS of CLONES with IDENTICAL HEAVY CHAINS
does the light chain rearrange 1 locus at a time or both? explain
one locus at a time
K rearranges first.
if unsuccessful, lambda locus is rearranged
light chains are able to produce _____ rearrangements. explain this
SUCCESSIVE rearrangements
if the first attempt fails, rearrangement occurs on the same allele until the gene segment availability is exhausted
what is the success rate of light chain rearrangement?
85% success rate
light chain successive rearrangements usually results in more ____ chains than _______ chains
more kappa chains than lambda chains
there is EXCLUSIVE lambda chain expression where?
IgD in upper respiratory tract
light chain rearrangement with K light chain on one chromosome was not successful.
explain the chain of events that happens now (successive rearrangement process)
we will move to K region on the other chromosome.
if this is also unsuccessful, we will recombine the lambda light chain
true or false:
the majority of the time, light chain rearrangement will be successful
true – 85% of the time
what is the second checkpoint?
can the new light chain form a functional B cell receptor with the mu chains in the ER?
at the time of the second checkpoint, are mu ready chains in the ER and ready to be assembled?
YES
If the second checkpoint is passed, (the new light chain can form a functional BCR with the mu heavy chain) what will happen?
the BCR will be formed
further assembly of Iga and Igb allows expression on the cell surface
this surface expression initiates signaling to HALT LIGHT CHAIN REARRANGEMENTS
If the second checkpoint is not passed, what happens?
(new light chain is not able to form a BCR with mu heavy chain)
the cell undergoes apoptosis
out of the 100 clones of small pre-b that were formed, around how many will become fully formed?
around 85
the expression of the BCR on the surface with a light chain and a heavy chain and all rearrangements are stopped.
what B cell is this?
immature B cell
all the heavy chains are ____ and all the light chains are ___
all the heavy chains are IDENTICAL and all the light chains are DIFFERENT
–diverse population of antigenically distinct B cells
