directed mutations

Violeta Stoyanova rumym at obzor.bio21.acad.bg
Wed Jan 21 11:45:47 EST 1998


Hypermutations occuring in the hypervariable regions (CDRs) of rearranged
immunoglobulin genes can also be regarded as "directed mutations". These
somatic mutations are triggered by binding of an antigen to the
corresponding antibody producing cell. Mutations in this case affect
predominantly those portions of the immunoglobulin which code for  the
antigen binding sites. As a result antibodies with higher affinity and
specificity of binding to the cognate antigen are generated. It is very
tempting to see Lamarcian evolution in this process. But what is still
required for defining them as "Lamarcian" is that mutations be not only
directed but also adaptive, i. e. mutations MUST ocuur which obligatorily
lead to improved antigen-antibody binding. So my question is:

Ia there any experimental evidence suggesting that naturally occuring
hypermutations in the CDRs are neutral (in Kimura's sense) with respect to a
posteriory established improved antigen binding properties of the antibodies?

Best regards!
Rumy




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