Toufic Renno trenno at
Mon Jan 31 18:33:45 EST 1994

>FORSDYKE at QUCDN.QueensU.CA wrote:
:>   Lee Wetzler suggested POSITIVE SELECTION as one of the "top ten"
: >developments in Immunology in the past 15 years. To avoid misunderstand-
: >ings, it might be useful  to get some agreement on what we mean by this
: >term.

:  >   SELECTION. In biology the word "selection" implies discrimination.
: >One may indeed select one chocolate from a box inwhich all chocolates are
: >identical, but here there is no discrimination. Selection in a biological
: >context means going to a box containing an assortment of different
: >chocolates and picking one out on the basis of some criterion ( I usually
: >go for the biggest).

:    > POSITIVE. If you fish in a "pool" with a net of a certain mesh then
: >you positively select fish which are bigger than the mesh size to take
: >home to market. Fish smaller than the mesh size are simply not affected.
: >They are NOT negatively selected against.

:   >  NEGATIVE. If you take the fish you have caught in the above net and
: >destroy them, then you have removed them from the available pool of fish.
: >Someone fishing subsequently with a net of smaller mesh than yours will
: >catch fish to take to market, but these will be of intermediate size
: >defined by the difference between the mesh sizes. Thus, because of prior
: >negative selection the available repertoire of fish sizes is diminished.
: >Negative selection is not the absence of positive selection.

: >This is pretty basic stuff. So perhaps all are in agreement?

:  >                Sincerely, Don Forsdyke,
:  >                           Discussion Leader. Bionet Immunology.

Nice analogy, and I agree that neg. selection is NOT a lack of pos. selection.
Where I differ is the conclusion that destroying the large fish removes
them (the Fishus largus species, not those particular fish that happened to
get caught) from the avilable pool. I contend that the extent to which the
pool of fish is affected depends pretty much on how long after having used
the first net you decide to go fishing again.  As long the large fish were
allowed to breed before they were removed, you will have more of them,
provided you wait long enough.

This is even more true for lymphocytes: since negative selection does not
affect lymphoid progenitors, more autorearective lymphocytes will be
generated AT THE SAME RATE AS BEFORE. The selective process just has to be
active all the time. This is especially true for B cells that are generated
throughout life.  Less T cells will be generated as the thymus eventually 
involutes, but this in no way is a result of selection.  Rearrangement 
(TCR or Ig) is a stochastic event, meaning that we don't know a priori
whether or not a receptor will be a candidate for negative selection. This
means that no amount of prior selection will affect the germline repertoire
at the time (which is all the time) it is contributing to the rearranged
receptor pool. 

Bottom line: the peceived decrease in negatively selectable lymphocytes is but
an optical illusion. 

Knock three times on the ceiling if you agree.  Twice on the pipe if the answer
is no.


Toufic Renno

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