Abstract
A WIDE range of immunosuppressive agents can facilitate the induction of specific tolerance by thymus-dependent antigens. In the case of Cyclophosphamide (CY), this involves T cells (including the generation of suppressor T cells), whereas B cells remain relatively unaffected1–3. On the other hand, CY lowers the B cell tolerance threshold to thymus-independent (TI) antigens4,5, a characteristic not shared by other alkylating agents (melphalan and chlor-ambucil) or immunosuppressive drugs (6-mercaptopurine, azathioprine and A-methopterin) (J. G. Howard and C. Hale, in preparation). Although high doses of CY induce selective depletion of B cells6,7, its immunosuppressive potential in vivo or in vitro is manifest with doses well below this cytotoxic threshold (F. L. Shand, in preparation), which is not the case with melphalan and chlorambucil. Consequently, the B cell tolerance-promoting and reversible immunosuppressive activities of CY might be dissociable from its cytotoxicity. We have investigated the ability of splenic B lymphocytes from CY-injected mice to cap and subsequently regenerate their surface immunoglobulin (SIg) receptors following treatment with anti-immunoglobulin. Re-expression of B cell SIg was grossly impaired following treatment with CY, but not with other immunosuppressive agents. This finding provides a possible explanation for the increased susceptibility of B cells to tolerance induction with TI antigens.
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SHAND, F., HOWARD, J. Cyclophosphamide inhibited B cell receptor regeneration as a basis for drug-induced tolerance. Nature 271, 255–257 (1978). https://doi.org/10.1038/271255a0
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DOI: https://doi.org/10.1038/271255a0
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