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

Abstract

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 microculture 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-reaetive 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 JgG production was the same as that of unfractionated cells, whereas the precursor frequency for JgM 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 (t to 2 doublings).

The Protection: The Unit of Humoral Immunity Selected by Evolution

“…This returns us once again to the assumption regarding the mechanism of LPS stimulation. If LPS stimulation is antigen-dependent, in that it acts on already activated B cells (aB) driving them to become effectors (eB) secreting Ig, or if LPS is a Signal[2] substitute and requires, in addition, that the B cell interact with antigen (Signal[l]), then the 20% of B cells LPS-stimulated in the unfractionated population would imply that FIT<0.2, again compatible with our estimate that FIT is of the order of O.L Whether or not LPS stimulation is antigen-dependent would not affect the conclusion that the B-cell population anti-SRBC studied by Martinez-Maza et al (1983) was antigen-selected. However, we agree with Bretscher (1978) that LPS stimulation is antigen-dependent (i.e., Signal[l]-dependent).…”

“…In one study (Martinez-Maza et al 1983), it was concluded that all B cells binding to SRBC were stimulable to effector cells secreting anti-SRBC. While this finding appears to be an example of the above-described effect of cryptic immunization, the study was actually initiated to test the curious idea that the theory of clonal selection requires that every ABC be functional.…”

“…The purified preparation, SRBC -ABC, had 82% ABCs, 87% Ig+ cells, so that 94% of the Ig^ cells were SRBC-binding. Using their most precise values (Table IV in Martinez-Maza 1983), we recast the data as shown in Table XIX.…”