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Extra resources for Annual Review of Immunology Volume 12 1994

Example text

Apart from Burnet’s ownbelief that the clonal selection theory merited a Nobel prize more than, or at least the same as, his other major immunological hypothesis [origin of tolerance], there is no doubt that his micro evolutionary explanation of the adaptive nature of antibody production heralded in a new era in immunology"(44, p. 140). To quote Burnet, "In that year (1949), Fenner and I published a second edition of an Institute monographon The Production of Antibodies. In this there wasthe first clear recognition that the differentiation of self from not-self was very important in immunologyand that, to a large extent, it was developed in birds and mammalsduring embryonic life.

Rev. Immunol. 12:1-62. org by HINARI on 08/30/07. For personal use only. ~’Seeref. 83for references. Lennox and I (83) concluded from genetic evidence and evolutionary reasoning that V and C had to be separate gene segments (then referred to incorrectly as cistrons) that were joined somatically as VCto produce the functional transcription unit or cistron. This unit was postulated to undergo somatic mutation to increase the size of the repertoire. It was inconceivable to us that the genomecould maintain as manyas 103 V-gene segments associated with 1 C-gene segment per locus in order to generate by random complementation 106 specificities (103 VLX 103 VH)but, admittedly, this was hardly an argument of substance.

However, we viewed the potential or total possible repertoire as quite degenerate. This implied to us that the loss of any given specificity could not be felt due to this degeneracy, and the "germline" encoded repertoire would have to shrink until loss had an evolutionarily selectable consequence. This wouldresult in a repertoire of inadequate size encodedin the germline. Only a somatic diversification mechanismto increase its size using this shrunken "germline" repertoire as a substrate would be impervious to degeneracy and, therefore, evolutionarily selectable.

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Annual Review of Immunology Volume 12 1994 by Annual Reviews


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