I wanted to throw out a question to see if anyone with a little more clinical or immunology experience might know the answer - Are there many (or any) knockout mutations of antibody light or heavy chains?
With the redundant nature of the chains, it seems that a single KO would have little phenotypic effect, but then, consequently, double KO offspring would be without antibodies - which doesn't, as far as I know, happen all that often.
The only phenotypic effects I could imagine would be a decline in the number of B-cells that develop viable antibodies (a ~50% reduction for a heavy KO, and ~12% reduction for a light KO, if my math is right), or a reduction in the potential antibodies due to a reduction in allotypic variation (eg, a mother and fathers V12 regions might be different), but neither of those effect seems like they would be evolutionarily disadvantageous enough for KOs to be entirely absent.
Also, if anyone feels like doing a little math, I calculated that ~17% of B cells would develop valid antibodies, but Prof. Cohen mentioned that only ~1/27 do. If the prob. of a single H chain working is 1/9 (since there are 2 recombinations) and a single L is 1/3 (since there's no D region):
(1-(8/9)^2)(1-(2/3)^4) = 16.9%
Is my math wrong, or my understanding of what's going on?
Thanks for any input...
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You know, I think you are right. I think I forgot that there is only VJ in light chains!
ReplyDeleteBut I need conceptual help: If the chance of one L chain allele rearranging correctly is 1/3, and you get 4 chances at it, what is the cumulative chance of at least one of these working? It is still 1/3, isn't it?
I think the easiest way to consider it is to look at the chances of it not working in any of them - for each L allele, there's a 2/3 chance of it not working, so cumulatively, there's a (2/3)^4, or 16/81 chance of no successful recombinations, leaving a 65/81, ~80%, chance of at least one working (though, in reality, you'll never get more than one).
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