need help with your account or subscription? click here to email us (or see the contact page)
join telegramNEW! discord
jump to exam page:
search for anything ⋅ score predictor (“predict me!”)
NBME 22 Answers

nbme22/Block 3/Question#5 (reveal difficulty score)
A 72-year-old man with multiple myeloma ...
Unrearranged immunoglobulin gene 🔍 / 📺 / 🌳 / 📖

 Login (or register) to see more

 +70  upvote downvote
submitted by sacredazn(101)

The concept is a convoluted way of asking if you knew how VDJ recombination works, which is that it is actually an example of altering the DNA of the B/T lymphocyte.

Southern blot technique: So when they use a probe against some region, and outputting a size of 1.5 kb or 6 kb, this is telling you the size of the DNA fragment in each cell (doesn’t matter if they say J probe or constant region probe, they’re just saying they’re targeting some nucleotide sequence found in the Ig locus/TCR beta chain locus respectively for B/T cells).

I think the confusing part could be wondering how you know whether you’re partly through rearrangement (answer choices B thru D) or if it hasn’t occurred at all yet (correct answer). Here, the concept is that B cells undergo V(D)J rearrangement in the bone marrow, while T cells do it in the thymus, and it all happens at once. So a plasma cell in the blood like in Multiple Myeloma would have fully undergone recombination, while a T cell in the blood could either be fully educated (and have finished VDJ recombination) or immature (hasn’t started VDJ).

Since the T cell gene was 6 kb and definitely bigger than the 1.5 kb gene, the T cell hasn’t undergone recombination yet.

 Login (or register) to see more
trichotillomaniac  very nice explanation! +29
nwinkelmann  This was awesome! Made so much sense and hopefully I will be able to think that critically about questions in the future (because I NEVER would have come up with this on my own, hah). +5
eacv  OMG! THANK YOU. I DIDNT KNOW ANYTHING about this!! Hope this is not testesd on real examen :p +5
ajss  wow! this explanation was awesome! thanks! +
mrglass  Also the T-cell V-D-J segments are not the same as the B-cell V-D-J segments. Therefore a B-cell J segment southern blot would look for whether the B-cell site VDJ segment in a T-cell, which would always non-rearranged. +6
mynamejeff  Thank you! So is this because multiple myeloma produces excessive monoclonal light chain Ig? Is this the 1.5 kb gene? Whereas, T-cells that have not gone through differentiation yet and their J region includes everything (VDJ) vs. just VJ in the light chain? (FA 2020 pg 104) +
peridot  This explanation is amazing! However, to fully understand another step of what the question is getting at, please take a look at @highyieldboardswards's and/or @mrglass' explanation as well - a very important addition!! +1
skonys  My logic was wrong but my answer correct. I am suffering from success. +
fhegedus  wow! this is amazing! thank you! +

 +18  upvote downvote
submitted by highyieldboardswards(18)

Short answer: All genes are present in both B and T cells, but they rearrange and express receptors that are specific to their lineage. Their are independent VDJ regions for B cell receptor generation and T cell receptor generation! This wiki article sheds light on this:

I too tragically missed this.. but it is actually so simple that we are missing the forest through the trees -- While both B and T cells undergo VDJ rearrangement, the V, D, and J genes are DIFFERENT GENES despite being organized and therefore classified in a similar fashion due to their shared need to generate diverse structures. To make matters more confusing, both sets of VDJ genes are on chromosome 14.

This is why the NBME specified that they are tagging THE SAME J REGION which is that of the B cell receptor gene J region, not the T cell receptor gene J-beta region (see wiki article). The B cell receptor gene is not rearranged in a T cell, if it was, T cells would have antibodies!

 Login (or register) to see more
redstrat  This. So much this! +1

 +5  upvote downvote
submitted by david_bball(5)

The way I thought about this question was that in MM there is a TON of antibodies being made, so the VDJ segment is being broken up/selected/rearranged many times and has been shortened to 1.5kb. As for the T Cells, that region isn’t being used (since there is no clonal expansion or selection) so it’s still got the full 6kb length untouched.

 Login (or register) to see more
d_holles  T cells still undergo VDJ recombination to form their TCRs. +7

 +2  upvote downvote
submitted by sam1(22)

While T cells do use the VDJ recombination, the T cell receptor chains are different genes from the B cell's heavy and light chains. Since they used a B cell J-region probe, the T cell's band will be much larger as this area of its DNA (the B cell heavy or light chain genes) have not been rearranged -- instead its T cell receptor genes have been rearranged.

 Login (or register) to see more

Must-See Comments from nbme22

sacredazn on Unrearranged immunoglobulin gene
seagull on Decreased binding of RNA polymerase
seagull on Anticholinergic
liverdietrying on Release of stored thyroid hormone from a ...
keycompany on Negative nitrogen balance
kernicterusthefrog on Displacement
mcl on Area labeled ‘D’
joha961 on Displacement
imgdoc on Area labeled ‘C’ (Abducens nucleus, right)
alwaysanonymous on 25 mL/cm H2O
drdoom on 1 in 600
seagull on Glutamine
bubbles on Acute retroviral infection
yotsubato on Phase variation

search for anything NEW!