NBME 22 Answers ↦
A 72-year-old man with multiple myeloma ...
Unrearranged immunoglobulin gene🔍
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:
https://en.wikipedia.org/wiki/V(D)J_recombination#T_cell_receptors
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!
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.
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.
submitted by sacredazn(59), 2019-06-01T21:31:04Z
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.