Date: Wed, 20 Jul 94 11:09:45 EDT
From: Don Forsdyke <FORSDYKE at QUCDN.QueensU.CA>
Subject: Re: Self/nonself discrimination
To: Ephraim Fuchs <ejf at welchlink.welch.jhu.edu>
In-Reply-To: Your message of Wed, 20 Jul 94 00:22:44 EDT
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Dr. Fuchs has agreed that the following exchange should be posted on his
behalf:
EJF:
I have a couple of problems with explanations of self/nonself discrimination
that state that only those antigens that are picked up in the form of Ag-Ab
complexes are presented.
1) There is strong evidence that dendritic cells, which do not express Fc
receptors, are the principal antigen presenting cells for naive T cells in
vivo. They do not usually capture antigens in the form of antigen-antibody
complexes. Rather, as immature dendritic cells they are able to capture
soluble antigens as efficiently as antigen-specific B cells (see Salusso and
Lanzavecchia, JEM, April 1994). Therefore, I do not see how they could
discriminate self from nonself on the basis of differential antigen capture.
DF: Correct. If a cell has NO Fc receptors and does NOT take up Ag-Ab complexes
then there is no basis for differential antigen capture based on recognition by
antibody. There is NO other GENERAL basis for extracellular recognition of
not-self. Thus, if it is true that the cell does discriminate, it must be
intracellularly. For a proposed basis of intracellular self/not-self discrim-
ination see Forsdyke 1994 (J.Theor.Biol. 167, 7-12).
EJF:
2) Even if the only antigens that are presented are those that first bound
antibody, then how do the B cells that make the antibody discriminate self from
nonself? That is, how do you ensure that only anti-nonself antibody is around
to bind antigen? A two signal model would say that signal 2 for B cells is
delivered by an antigen-specific T cell, but then we are back to the problem
of how the T cell discriminates self from nonself.
DF: Yes, "A" two signal model would say that signal 2 is delivered by antigen-
specific T cells. So perhaps the model you invoke is wrong. An ALTERNATIVE
two signal model does not require T cells for education of nascent B cells
(see Forsdyke 1992 J.Theor.Biol. 154, 109-118).
Sincerely, Don Forsdyke
Discussion Leader. Bionet.immunology
