B cell subsets, idiotype selection: positive selection for some B lymphocytes?
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Biomedical subjects
Publications and source records attributed to A Van Acker.
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Monitoring with anti-idiotypic sera has been applied to identify tumoral cells in a myeloma patient still alive in complete remission 9 years after diagnosis. Monoclonal plasma cells displayed a labeling index that decreased in complete remission below 1%. The great majority of B lymphocytes belonged to the tumoral clone even in complete remission and were therefore not affected by conventional chemotherapy. Some aspects of this myeloma patient are discussed in the light of these immunologic and kinetic findings. In addition, it is suggested that the therapeutic management of the complete remission should be re-examined, by considering a lymphocytolytic therapy.
Suppressor T cells have been shown to be much more radiosensitive than other lymphoïd cells, and we have tried to reduce tumor growth by low-dose irradiation. Syngeneic DBA/2 mice received whole-body irradiation (150 rads; 1 rad = 0.01 J/kg) 6 days after P815 tumor inoculation. Tumor growth is significantly reduced in mildly irradiated mice. We also attempted to reduce syngeneic tumor growth by raising immunity against suppressor T cells in two different systems. DBA/2 mice were immunized against splenic T cells collected after disappearance of cytotoxicity and then injected with P815 tumor cells. These mice develop a very high primary cytotoxicity against P815 cells. C57BL/6 mice were immunized against blastic suppressor T cells, before injection of T2 tumor cells. Some of these mice reject the tumor and other develop smaller tumors than control mice. These results could be explained by the induction of antiidiotypic activity directed against the immunological receptors of suppressor T lymphocytes, because immunization with blastic suppressor T cells from mice bearing the T2 tumor does not modify the growth of another tumor, T10.
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Rabbits hyperimmunized with tobacco mosaic virus synthesize very heterogeneous antibodies. Despite this, specific anti-idiotypic sera recognizing a large part (70%) of these antibodies can be raised in rabbits matched for allotypic specificities a1, a2, a3, b4, b5, b6, c7, and b9. Different rabbits synthesize antibodies with different idiotypic specificities. However, in the serum of a single rabbit antibody fractions of different isoelectric pH share some idiotypic specificities. The results show that, at least in certain cases, antibodies against one antigen are not simply a random collection of immunoglobulin which happen to fit with this antigen, but that some definite relationship exists between the products of different clones which have been activated by antigen. These findings are discussed in the light of network concepts of the immune system.
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We have studied seven human monoclonal gammopathies using anti-idiotypic sera. In benign and malignant gammopathies, we have observed a similar number of B lymphocytes bearing idiotypic specificities also found on the monoclonal protein. These observations suggest that the plasma cell population is only a phenotypic expression of a tumoral event occurring in a B lymphocytes precursor which can still completely differentiate. In four myeloma patients and one benign monoclonal gammopathy, we also observed T lymphocytes bearing receptors idiotypically cross-reactive with the monoclonal protein. The values ranged from 1.8 to 8.0% within the purified T-cell population. In a first hypothesis, these T lymphocytes can belong to the tumoral clone itself. The tumoral event must occur at the level of a common precursor not yet determined to B or T pathway of differentiation. In a second hypothesis, these T lymphocytes are not cancerous but are induced by a strong perturbation of the idiotypic network, due to the enormous amount of the idiotypic B-cell tumoral subset.
Irradiated rabbits grafted with allogeneic lymph node, spleen and bone marrow cells from a donor rabbit hyperimmunized against TMV synthesize high affinity antibodies, displaying mainly recipient allotypic specificities, after antigen boosting. By contrast, recipient rabbits from non-immune donors synthesize antibodies of lower affinity. It is suggested that the differentiation of new emerging host B cells is specifically influenced by the presence of donor-memory cells.
Irradiated rabbits were grafted with a mixture of bone marrow, lymph node and spleen cells from donors hyperimmunized against TMV. Recipient and donors were characterized by different a allotypic specificities. Antibodies synthesized in the recipients display allotypic markers from the recipients but idiotypic specificities cross-reactive with those of donor antibodies. The results show that the differentiation of new host B cells is influenced by the presence of donor memory cells and are interpreted in the light of network concepts.