B-Cells - Why one specificity?

John Richard Seavitt jrseavit at artsci.wustl.edu
Fri Dec 12 12:19:20 EST 1997

On Fri, 12 Dec 1997, Andrew Louka wrote:

> The question asks "why", and not "how do B cells achieve one specificity". 

> I think that these reasons make a lot of sense, but is it the whole 
> story?  Does evolution play a significant role?

Okay...the short (and, admittedly, wise-assed) response that includes
evolution in it is that of course evolution plays a role in it, and that
the reason 'why' there's just a single specificity is that this system
developed, and it hasn't been selected against.  Yet.

I think some points have been brought up that describe the molecular
mechanisms of dna rembination that leads to antigen receptor generation,
the molecular mechanisms of signal transduction by antigen receptors.
Additionally, I'll add that I think the mechanism of class switching is
worth thinking about in this context.

But none of the research leading to our understandings of these mechanisms
is meant to answer 'why'.  It's meant to describe the system as it is
(and, as pointed out, alpha chain allelic exclusion on T cells may NOT be
so rigorous), and to determine the mechanisms that make it so.  We can
also design experiments to ask how we can manipulate the existing system,
presumably for therapeutic reasons.

It is not within our knowledge to design experiments that ask 'why' in
this regard.  We don't know whether other systems COULD have evolved, and
it will be a long time before an experiment could be designed to ask such
a question.  Sure, we can make up stories that 'make a lot of sense' based
on what we KNOW, but that's not science, and you won't find it in the
scientific literature.  Unless you can TEST the story with an experiment
that has an outcome that can rule out the possibility that your story is
wrong, you publish it as 'fiction'.  Erudite types might call it
speculation, but it's still a duck.

I make this point to explain that there's a sensible reason that there's
nothing in the textbooks or literature.  It's certainly a good thinking
exercise, and there's data that consistent with some 'good stories' we
could come up with.  But whatever we say, it's just a story.

John Seavitt

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