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Antibody‐Secreting Cell Precursor Frequencies among the Sheep Erythrocyte‐Binding Cells of Non‐Immune Mice

The clonal selection theory, as formulated by Burnet, predicts that a lymphocyte bearing receptors for a given antigen will, upon activation, produce antibody to that same antigen. This prediction has for the first time been quantitatively confirmed, by precursor frequency analysis of highly purified sheep erythrocyte antigen‐binding cells (SRBC‐ABC), isolated from the spleens of non‐immune mice, by means of an LPS‐driven limiting dilution micro‐culture system. These precursor frequencies indicated that virtually every non‐immune SRBC‐ABC that was a precursor for the secretion of IgM (or IgG) was also a precursor for the secretion of SRBC‐specific IgM (or SRBC‐specific JgG), after correction for non‐SRBC‐ABC B cells contaminating the SRBC‐ABC preparations. These data help to clarify the relationship between antigen‐binding cells and the antigen‐reactive cells of the clonal selection theory. In the course of making this observation, it was also shown that the precursor frequency of purified non‐immune SRBC‐ABC for IgG production was the same as that of unfractionated cells, whereas the precursor frequency for IgM production and LPS‐induced thymidine incorporation were both lower in the ABC. The clone size estimates for IgM and IgG precursors in ABC and unfractionated cells all fell within a narrow range (1 to 2 doublings).