old thymus, new receptor question

Dr. Colin R.A. Hewitt crah1 at leicester.ac.uk
Fri Jan 21 12:29:07 EST 1994


When I said that 

> if the thymus,  or another organ did not do the job of sorting useful from useless 
>and harmful, we would all be full of lymphocytes with no useful function at all."
I was really speculating on what would happen if all pre-thymocytes that left the 
bone marrow WERE to mature and enter the periphery.
If there were no organ of selection, all cells that left the bone marrow would mature, 
(including the 90% plus that normally die), this would surely leave useful cells at 
such a low clonal frequency that the repertoire of useful cells would be ineffective. It 
clearly isn't, so the point was, that there must be a surrogate thymus active in 
adulthood.  
Your point about the importance of PCD is understood, but if you dont have a fully 
functional thymus you can neither negatively select to prevent the spillover scenario 
above, nor rescue cells from death ( positive selection. )So the question still stands: 
If we continue to make potentially harmful and useless receptors till the day we die, 
where is all their education going on in the absence of a fully functional thymus.
Peripheral tolerance is now well accepted, what about peripheral positive selection?

Surely the Raff model would only work  in a static organ like a brain or liver, In a 
dynamic organ like the immune system, surely the cells don't stay still long enough 
for them to respond to a gradient of survival factor. Wouldn't his model also require 
the existence of a specialised cell that produces the survival factor. If for a liver this 
were located say in the centre of a liver, would it not imply that liver cells on the outer 
surface of the organ would always be dieing with a "germinal centre" of high survival 
in the centre?


Dr. Colin R.A. Hewitt
University of Leicester/MRC
Centre for Mechanisms of Human Toxicity
Hodgkin Building
PO Box 138
Lancaster Rd
LEICESTER
LE1 9HN
U.K.

Phone +44 (0)533 525587
Fax +44 (0)533 525616
E-Mail crah1 at le.ac.uk.



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