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
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
PO Box 138
Phone +44 (0)533 525587
Fax +44 (0)533 525616
E-Mail crah1 at le.ac.uk.