Annual Review of Immunology Volume 12 1994 by Annual Reviews

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Rev. Immunol. 12:1-62. org by HINARI on 08/30/07. For personal use only. ON THINKING AND WISDOM 45 role as part of the whole and as a way to estimate the limits on its parameters. That camemuchlater (4, 25). Second, the STAGEI (high copy number) repertoire was somatically varied by mutation to yield the STAGE lI (low copy number) repertoire. This was demonstrated unambiguously by Weigert et al (90) in 1970. The logic of this experimentis so elegant it is worth summarizing. Weknewby direct assay, that the ~:2~ ratio in murine serum was ~ 30:1.

For everyoneto havebeena little bit right implies that, today, there is a completelack of awarenessthat the origin of the repertoire has no correct conceptualization. Thusthere is no wayto tell whichlittle bit wasright. No matter whowas a little bit right, everyonewasa wholelot wrong;and it is fromthe wholelot wrong that welearn. Themajor methodologicalproblemis two fold. First, mostof "the little bits that wereright" wereguesses, not argued or reasonedchoices betweenalternatives and, therefore, often presented in the wrongcontext.

The delivery of Signal [2] to innocent bystanders must be minimized. " This was Annual Reviews Annu. Rev. Immunol. 12:1-62. org by HINARI on 08/30/07. For personal use only. 36 co~4y postulated to be of a special class, lgT, the function of whichwas to initiate Signal [2]. Our 1968 proposal (47) for Signal [2] was conceptually wrong. e. the stretched conformation). This proposal that the BAr could undergo two distinct conformational changes corresponding to the two signals was conceptually wrong because it is central to the theory that Signal [1] be included in the inductive event (Signals [1]+[2]) and not an alternate state.

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