The immunogenesis of the human fetus has been investigated by means of the formation of immunoglobulins in vitro, immunofluorescence, morphological studies, and analysis of the immunoglobulins in the serum. Twenty fetuses which were born alive but died soon after delivery, were studied; their ages ranged from 13 to 31 weeks. The results of the spleen cultures demonstrated the synthesis of IgG and IgM, which starts at about the twentieth week of gestation. In the serum, IgM could be detected at about the same period. The immunofluorescent staining of the spleen tissue showed that medium sized and large lymphoid cells as well as plasma cells, even with Russell bodies, were positive for either IgG or IgM. The peripheral blood was also found to contain a small number of medium sized IgG and IgM-positive cells. Both the spleen and the peripheral blood showed a considerable number of fluorescent small lymphocytes which exclusively contained IgM. The relatively high ratio of IgM to IgG production prenatally as compared to the postnatal situation, agrees with a predominantly primary antibody response in fetal life. In general, the fetal thymus did not synthesize immunoglobulins. No indications for the synthesis of IgA and IgD during fetal life were found.

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Cell suspensions enriched and depleted for rosette-forming cells with sheep red blood cells (E-RFC) and depleted for RFC with antibody complexes were prepared. The isolated fractions were characterized by cell surface marker analysis and tested for their natural killer (NK) and killer (K) cell activity against K-5 62 cells and IgG-coated P-8 15 cells, growing in suspension, and against a number of monolayer tumor cell lines. It was found that the NK cells most likely belong t o the T cell lymphocyte subpopulation. Furthermore, this study indicates that several subpopulations exist, e.g. NK cells that have no IgG F c receptor (FcR) on their surface and NK cells that bear IgG FcR, indicating that for a proportion of NK cells the IgG FcR is not involved in the NK lytic process and hence antibody-independent. Moreover, monocytes and B lymphocytes appear not t o be directly involved in the NK cell lytic process.Furthermore, cell separation procedures were used t o obtain cell suspensions either bearing IgG FcR or lacking IgG FcR. Cells bearing IgG FcR were isolated in such a way that they lost their IgG FcR by shedding, as a result of the separation procedure. Again, all fractions were simultaneously characterized by cell surface marker analysis and tested for their NK and K cell lytic activity. The effect of immune complexes on the NK and K cell lytic activities was investigated. The data indicate that the IgG FcR is not involved in the NK lytic mechanism, although this receptor may be present o n the NK cell. Moreover, prolonged culturing of lymphocytes increases and/or induces NK cell lytic activity.

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