B-Cells - Why one specificity?

mdoherty mdoherty at atlas.niaid.nih.gov
Mon Dec 15 16:28:06 EST 1997


In article <Pine.SUN.3.91.971212110103.26624B-100000 at loki.brunel.ac.uk>,
Andrew Louka <bb95asl at brunel.ac.uk> wrote:

> > If you are interested in immunology, the answer is very complex. Why do
> > not you read the "Maturation of B cells" chapter of any Immunology
> > textbook? If I recall correctly  there are English textbooks available.
> 
> I'm studying applied biology and have to write an essay titled "One B 
> cell, one specificity.  Why.".  I've read chapters of different 
> immunology books, and a few reviews that I have been cited from kind 
> people after my posting to Usenet, but am barely enlightened.
> 
> The question asks "why", and not "how do B cells achieve one specificity". 
> Restricted cell surface area and the inability to effect a directed
> response (if the cell carried several different receptors, it would not be
> able to differentiate between them when one binds an antigen.  It would be
> inefficient to manufacture lots of different antibodies) are the most
> relevant suggestions yet.
> 
> I think that these reasons make a lot of sense, but is it the whole 
> story?  Does evolution play a significant role?
> 

Right, well first up I'll admit I don't know "why" - and I doubt anyone
else does either.  You can only test "how" and speculate about "why".

However, given that we can make informed guesses (and that's as good as it
gets).

My guesses would be:

1) while some autoreactive lymphocytes do survive to escape into the
periphery, this is niether common, nor, one suspects a good thing.  To
allow your B cells to express multiple specificities would mean expressing
them all at the time of selection and would almost certainly lead to a
greater proportion of your B cells ending up in the trashcan. That's a
significant waste of resources, and we know that evolution is pretty strict
with those who waste resources.

2) Following up on this, B cell genes are fitted together to generate
specificity by excising and tossing away the portions not used.  To get
multiple specifities out of this, you would either have to evolve another
method of generating multiple specificities from the same germline genes,
or you would have to carry multiple copies of the antibody-encoding genes. 
Either way, that means more genes must be carried again in every cell and
they would have to provide a significant benefit to offset the energy
"drag" involved in teir maintainance.

3) and following up from 2) - what significant benefits?  While the range
of specificities is theoretically very large, your body only has carrying
space for so many B lymphocytes.  When you get infected/exposed, *only*
those lymphocytes which have the correct specificity to recognise the
antigen are activated and proliferate.  However, not *all* B cells which
potentially recognise an antigen proliferate and prosper.  Those who can
outcompete (ie those with the most exquisite sensitivity) are the ones who
seem to come to predominate.  What real advantage would multiple
specificities confer? Sure, you could carry more specificities on a lower
number of cells - but you would end up with the same number of cells anyway
- there are more possible specificities than there are places to put B
cells, even granted multiples on one cell.  Moreover, there's no way to
tell how many cells are enough?  The body has no way to tell what it has
already generated.  Finally, in any response, the hypothetical
multiple-specificity animal is *still* going to select for the few best
antibody producing cells - so will end up with a limited repetoire aimed at
the immunodominant epitopes.

In other words, there's no big apparent benefit to carrying those extra
genes, so presumably evolution has pared us down so we make the smallest
possible expenditure for the best coverage.

Remember of course that this is a just so story explaining why things are
the way they are.  If they were otherwise, I'd be writing to explain why
they couldn't be any other way.

The B cell/ T cell system is pretty damn well preserved among many 'higher"
vertebrates, which suggests a common ancestry - but this implies in turn
that it may have simply been selected long ago and retained just because it
works - not because it is the best system.  Evolution is like the free
market.  It doesn't design systems, it cobbles them together out of what's
available at the time.  So what you get is something that's workable - not
necessarily elegant.

Cheers, Mark



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