The immunosuppressant 15-deoxyspergualin [correction of 1,5-deoxyspergualin] reveals commonality between preT and preB cell differentiation.
15 [correction of 1,5] deoxyspergualin (DSG) is a potent immunosuppressant whose mechanism of action is still somewhat of a mystery. We have studied the generation of lymphocytes in mice treated with this drug. The differentiation of T cells in the thymus was blocked at an important early control point: the CD4-8- --> CD4+8+ transition, known to depend on the expression of a preTCR complex that includes the variable TCR-beta, but not TCR-alpha, chain. In clear contrast, a later control point, the CD4+8+ --> CD4+8- or CD4-8+ transition, dependent on the display of a conventional alpha:beta TCR complex, appeared unaffected, as did activation of mature T cells both in vitro and in vivo. Interestingly, preB cell differentiation in the bone marrow was blocked at a precisely equivalent point: the A-C --> C' transition, controlled by expression of a pre-receptor complex containing the Ig heavy, but not light, chain. Mature B cells seemed unperturbed. These findings have theoretical implications, suggesting common signaling pathways in early lymphocytes that are distinct from those employed by more mature cells, and are also of practical interest, to be considered in the design of DSG treatment protocols.
Wang
B
B
Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), de Strasbourg, France.
Benoist
C
C
Mathis
D
D
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D005333:Fetus; D005434:Flow Cytometry; D006146:Guanidines / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009924:Organ Culture Techniques; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000187:drug effects / Q000196:embryology / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D006146:Guanidines; D007166:Immunosuppressive Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta; C037258:gusperimus