Alberto J. L. Macario ¹, Everly Conway de Macario ¹, Claudio Franceschi ¹, and Franco Celada ¹

¹ From the Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden, and the Laboratory of Cell Biology, Consiglio Nazionale delle Ricerche, Rome, Italy

We have cultivated lymph node microfragments from ß-D-galactosidase (Escherichia coli) primed rabbits and have measured their secondary response directed towards the whole molecule (precipitating antibodies) and to a single determinant (activating antibodies) of the antigen. By decreasing the size of the fragments to 10⁵ cells, we began to observe heterogeneity among identical cultures in terms of positivity of response, antibody specificity, and titers. The affinity of "early" activating antibodies was inversely proportional to the dose of challenge. While no maturation was seen in low and excessive challenge, in all cultures receiving intermediate doses the association constant was raised several orders of magnitude within periods of 20 days. The relevance of these data to the mechanism of affinity selection of antigen-sensitive cells is discussed.

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• Segre, D., Segre, M. (1973). Failure of Limiting Antigen Doses to Selectively Stimulate High-Avidity Memory Cells. Science 181: 851-853 [Abstract]  

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