B-Cells - Why one specificity?

Dr. Bernhard Kleine bernhard.kleine at medizin.uni-ulm.de.nospam
Wed Dec 17 16:52:44 EST 1997


In message <Pine.SUN.3.91.971212112146.26624C-100000 at loki.brunel.ac.uk> - Andrew Louka
<bb95asl at brunel.ac.uk>Fri, 12 Dec 1997 11:44:17 +0000 writes:
:>
:>Hi Mike,
:>
:>Thanks for your comments and review of the thread to date.  The question
:>of "B-cells - why one specificity" seems to be one for which there is no
:>commonly accepted answer.  This may be because, as I found in the first
:>responses to my original posting, that most people assume the answer to be
:>documented, and furthermore, may not consider the matter to be of
:>fundamental importance (not a reflection of those participating in the
:>current thread!). 
:>
:>I myself, however, am under the impression that the more we understand 
:>of the basics, the easier it becomes to understand the advanced questions 
:>of the science in question.  Indeed, one of the "tricks" for inviting 
:>serendipity is being able to recognise a happy discovery when you see one - 
:>made easier by an understanding of the basics, or fundamentals of the 
:>field.
:>
:>Andy
:>
:>
:>[SNIPPIT]
:>
:>On Wed, 10 Dec 1997, Mike Clark wrote:
:>
:>> In article <Pine.SUN.3.91.971209120117.977D-100000 at ccsp-23.brunel.ac.uk>,
:>> Andrew Louka <URL:mailto:bb95asl at brunel.ac.uk> wrote:
:>> > Why one B cell, one specificity?  Why not have multiple specificities per 
:>> > B cell - surely this would have been more effective (and energy efficient!).
:>> > 
:>> > I'd appreciate any comments or explanations :-)
:>> > 
:>> > Thanks,
:>> > Andy
:>> > 
:>> Hi Andy,
:>> I've frequently thought about this problem when discussing T and B cell
:>> receptors with my students. Although it's always difficult to prove a
:>> particular hypothesis with regard to an evolutionary perspective I can make
:>> the following points which I think are relevant.
:>[Contd...]
:>
:>--
:>url     : http://www.brunel.ac.uk:8080/~bb95asl/                      
:>O-
:>
Nice thread!

Having read the discusssion I missed one point: As long as no Ig is functional on the cell surface,
the B cell is driven to divide. Once Ig is made the cell comes to rest and does not divide any
further. This looks to describe the "how" but turns out to describe the "why".
You should remember that the process of genetic rearrangement leads to functional heavy and light
chain genes only in one out of six arrangements i.e. 84 % of rearrangements are wasted including all
the cell divisions where no rearrangement takes place. 
It is therefore for pure economical reason that having finished one Ig the cell stops all activity
to make another one. She may also become confused e.g. when nonfunctional rearrangements take place
in addition to previous functional ones: Should she become apoptotic or bear the nonfunctional
rearrangement?
The invention of genetic rearrangement is also one nice example of the economy of evolution: The
genome contains information for myriads of antibodies in the smallest possible loci. Before Tonegawa
found rearrangement it looked that the whole human or nonhuman genome must have been used to code
for all the theoretical 10^11 antibodies. Other theories were even more bizarr.

Having written this I still wonder whether scientist should engage on answering "why"-questions in
cases where no experimental evidence is possible. Such question are for the kinds regarding the
world's wonders innocently with very large eyes. A scientist engaged in such a discussion is
trapped. Why is evolution economical? may serve as an example and is pulling my own leg (see above).
Instead of testing whether this is indeed the fact something which surpasses the resources of even
the largest institute I guess, looking for an answer to the "Why" question also assumes that economy
is intended by evolution and there is no way to meet the one who had that intention.

Coming back to the Why-one-specifity-question I feel that this type of question implies that the
evolutionary process aimed at rearranging just single immunoglobulin per cell (teleology). Such a
thinking is fundamentally wrong IMHO. The only answer to the question is: because it had happened
that way. Or do you really think that individual mutations, gene duplications, gene conversions etc.
all happened to achieve finally the goal of a single Ig receptor on a B cell. You would be seing
GOD's hand pulling away one base and substituting it with a wrongly paired one. Nice cartoon BTW.

I think scientifically sound questions should be solved in a scientific way. I am eager to discuss
this issue further.

All the best

Bernhard Kleine
(bernhard.kleine at medizin.uni-ulm.de)
When replying, please remove the nospam measure from my email address! 




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