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Why do TCR's not undergo hypermutation

by FunkyDwarf
Tags: hypermutation, undergo
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FunkyDwarf
#1
Mar10-14, 03:44 PM
P: 479
Hello!

I have a question regarding the development of B cells vs T cells.

Specifically, I understand that the development of the T cell receptions and antibodies on the Bcells are very similar up to the point of activation. Both undergo somatic recombination to generate diversity, but then B-cells go through an extra phase with somatic hypermutation to increase affinity.

One argument as to why T-cells don't go through this second phase as well is that it may cause them to increase their affinity for self-peptides and thus become dangerous (given that they already passed negative selection it would be like letting someone 'make' a gun once through a metal detector). Thus by ensuring the helper T-cells that don't bind to self are the ones activating B-cells, we ensure that the B-cells (having receptors for the same antigen as the t-cell) won't go out and proliferate and bind to self peptides and cause auto immune problems.

However: what's to stop somatic hypermutation in the B-cells from giving rise to antibodies that can bind to self? If the possible range of binding is so huge that it is a risk for T-cells, why is it not also a risk for B-cells? (i.e. to mutate to bind well beyond their original antigen profile)

Thanks!

EDIT: ok it makes a bit more sense on I realised that the activation comes from T cells both before and after hypermutation, meaning that a T-cell would have to present a self peptide in order to proliferate a nasty B-cell. But then the question becomes: isn't the bottleneck still the affinity of the TCRs? Or is it just a matter of 'assume the TCR can bind at some point to the antigen, lets make sure that antibodies are faster/better'?
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