Resistance of pokeweed mitogen-stimulated B cells to inhibition by deoxyadenosine.
Deoxyadenosine (dAdo) levels above 2 microM inhibit plasma cell (PC) differentiation by human blood lymphocytes in pokeweed mitogen (PWM) stimulated cultures containing deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase (ADA). ADA inhibition by dCF alone did not suppress PC differentiation. Thymidine uptake by T cell blasts continuously cultured in conditioned medium was inhibited by dAdo and dCF; two of five EBV-infected B cell lines were also inhibited while three were resistant. Inhibition of PWM-induced PC differentiation of B cells by dCF and dAdo was reversed when conditioned medium (a source of T cell helper factors) was added to the cultures, and dAdo and dCF added to PWM-stimulated cultures 48 hr after their initiation did not inhibit PC differentiation, though thymidine uptake and the total number of cells recovered from the cultures were reduced. Removal of T cells after 48 hr of culture slightly reduced the numbers of PC in PWM-stimulated lymphocyte cultures but no further inhibition was obtained when dCF and dAdo were added to these T-depleted cultures, nor was their thymidine uptake further reduced. These results suggest that the in vitro suppression of B cell differentiation by dAdo in PWM-stimulated cultures is not due to direct toxicity of purine nucleosides to B cells but may be due to interference with T cell help. This is consistent with the view that a relative lack of helper activity by T cells contributes to the antibody deficiency of patients with ADA deficiency.
D000241:Adenosine / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology; D003839:Deoxyadenosines / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects; D015649:Pentostatin; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D013936:Thymidine / Q000378:metabolism
D003839:Deoxyadenosines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011043:Pokeweed Mitogens; D003070:Coformycin; D015649:Pentostatin; D000241:Adenosine; D013936:Thymidine