Biomedical subjects
Publications and source records attributed to A J Cunningham.
The development of functionally mature B cells in the liver and spleen of fetal and neonatal CBA mice has been followed. A mature B cell is defined as one giving rise to antibody-producing progeny within 2 days in culture. Very few such B cells are found during fetal life. After birth there is a rapid rise in the numbers reaching 1/3 of adult levels in the 7-day-old spleen.
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This paper maps the developmental stage reached by B cells in mouse fetuses of different ages. The "maturity" of these cells was assessed in a functional way by measuring the time taken for cells to generate antibody-forming progeny when injected into carrier-primed irradiated adult hosts and challenged daily with antigen. A steady uninterrupted progression in development of B cells occurred between 13 days of gestation and birth. There was no evidence for a stage during which B cells could only be paralyzed and not induced by antigen.
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Previous experimental work demonstrated that clonal variation occurs in vitro. The present experiments were designed to test for clonal variation in vivo. B cells were transferred at limiting dilution, with antigen, into irradiated recipients. Seven days later spleens were assayed for plaque-forming cell (PFC) colonies. Control experiments showed that these PFC colonies were clones, that is, they were derived from a single B cell precursor. When the clones were analyzed for heterogeneity of the PFC population, using cross-reactivity on various mixtures of red blood cells as a method of detecting differences in antibody specificity, from 23-83% of the clones contained variants. By adjusting the amounts of helper activity and antigen available to a developing clone, we have been able to influence this variation; high levels of help and/or antigen favor pure clones, while low levels of either produce mainly mixed clones.
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Allogeneic reactions have conventionally been considered as typical immune responses by one population of cells to antigens present on the other. This view is inadequate, since it does not explain many features of these reactions, among which are: (1) reactivity is much higher between different strains within a species than between species, in spite of the much greater antigenic disparity in the second case; (2) a very high proportion of cells may respond to allogeneic stimuli; (3) major histocompatibility differences are not essential for vigorous allogeneic reactions; (4) the responding population need not be immunologically competent to respond to antigens of the stimulating population; (5) the stimulating population must be both metabolically active and immunocompetent. We have tried to produce a model of cell interaction which will account for these and other anomalies, which at the same time explaining both normal antigenic stimulation (through cell-cell cooperation) and allogeneic interactions as examples of the same basic mechanisms. The model is based on the Bretscher-Cohn scheme of cell interaction. An allogeneic reaction is seen as having two stages: (1) Cells come together when antibody receptors on cells of one population combine with antigens on cells of the other. To this extent, our model is the same as the conventional one. It need not be the responding population which has the receptors, however. (2) A species-specific proliferation signal passes between the cells. This is the same signal as is involved in normal antibody induction. Even antigen-receptor bonds which are very weak may result in effective stimulation of one or both partners because of enhancing effect of this signal, and because the antigens involved are probably repeated over the cell surface, enabling multipoint binding. This explains the very proportions of cells which proliferate. The exact outcome of any allogeneic interaction will depend on which of the two populations have antibody receptors for antigens on the other, which can produce the proliferative stimulus, and which can respond to either the proliferative signal alone or to this stimulus plus antigen.
The technique of adoptively transferring an immune response by injecting donor cells into irradiated recipient mice is based on the assumption that the host is rendered immunologically inert by irradiation. We present evidence that these mice are not inert; in the presence of donor cells of various types they mount a substantial immune response against both heterologous erythrocytes and dinitrophenylated bovine serum albumin. This restoration of the host requires donor cells for its expression and can account for up to 100% of the total response. The problems associated with this finding are discussed.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.