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HERE. RB 1st mutation(already+) 2nd mutation

SPORADIC RB Intact alleles Both spontaneous mutations in retinal cell

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submitted by sacredazn(59),

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! +7  
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). +4  
eacv  OMG! THANK YOU. I DIDNT KNOW ANYTHING about this!! Hope this is not testesd on real examen :p +3  
ribosome01  I would like to meet you personally and say thank you I wish I had a teacher like you +  
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. +4  
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!! +  

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