I disagree with the assumption that antigen receptor generation is a
completely random process, particularly in younger and fetal mammals.
A fairly large number of reports (including our own) have shown that
fetal rearrangements can be quite distinct from those in later life:
In the TCRbeta locus and in the Ig heavy chain locus, fetal
rearrangements are characterized by a marked *lack* of N-region
addition at the gene segment joints AND there is preferential usage of
certain gene segments. One school of thought is that the antigen
receptors during early life tend to be self-reactive and that these
"germline" rearrangements (i.e. no somtaic mutation lack of N-regions
etc) bias the reopertoire towards self-reactivity. While we don't know
the fate of the cells bearing these type of receptors, we can speculate
that they are involved in the induction of tolerance towards
self-antigens.
> A recent post stated:
>> I can see that the rate of antigen experience by T cells is
> greatest when younger, but this ignores the fact that new TcR and Ig
> are generated right up until the day you die. Since antigen receptor
> generation is essentially a random process it is inevitable
> that cells with self-reactive receptors will emerge from the bone marrow
> all throughout life. If the thymus involutes after
> puberty, where are all these new cells getting their education
> (both in +ve and -ve selection)?
>>> Is this really a problem? If the thymus involutes, then
> no T cells will be made i.e. no positive selection.
> As no T cells are made, it does'nt matter that there
> is no negative selection either.
>>>
==============================================================================
James F. George, Ph.D.
Department of Surgery
University of Alabama at Birmingham
205-934-4261 voice
txpljfg at uabcvsr.cvsr.uab.edu
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