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NBME 22 Answers

nbme22/Block 3/Question#5

A 72-year-old man with multiple myeloma agrees to ...

Unrearranged immunoglobulin gene

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submitted by sacredazn(18),

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.

trichotillomaniac  very nice explanation! +3  
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). +1  

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submitted by david_bball(3),

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.

d_holles  T cells still undergo VDJ recombination to form their TCRs. +  

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submitted by sam1(0),

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.