Enhanced antibody response in the presence of partial adenosine deaminase inhibition.
The enzyme adenosine deaminase (ADA) catalyzes the conversion of adenosine and 2'-deoxyadenosine to inosine and 2'-deoxyinosine, respectively. In the absence of ADA activity, 2'-deoxyadenosine is phosphorylated to deoxyadenosine triphosphate. This study concerned the effects of the ADA inhibitor 2'-deoxycoformycin on the murine in vitro immune response to sheep red blood cells (Mishell-Dutton cultures). In the presence of 10(-7) M 2'-deoxycoformycin or 1 mM 2'-deoxyadenosine, there was a significant increase in the plaque-forming cell response when calculated as plaques per 10(6) viable cells recovered. Cultures containing 10(-7) M 2'-deoxycoformycin retained approximately 10% of residual ADA activity of control cultures. Partial ADA deficiency was not preferentially toxic for cells capable of suppressing plaque cell generation. However, there was a decrease of recovered viable cells in all ADA-deficient cultures. There was no change in the percentage of recovered cells which were L3T4+ or Lyt 2+. A significant decrease was observed in a population of cells expressing surface immunoglobulins. The number of plaque-forming cells/10(3) recovered B cells increased significantly. We conclude that partial ADA deficiency results in selective toxicity to a population of non-antigen-specific B cells. Further studies with antigen-specific cells are necessary to determine the possible mechanism(s) by which cellular activation may prevent susceptibility to the toxic effects of ADA deficiency.
Hoffman
E A
EA
Department of Microbiology, Marshall University School of Medicine, Huntington, West Virginia 25755-9330.
Kopp
W C
WC
Moat
A G
AG
D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology; D005260:Female; D051379:Mice; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D058892:Adenosine Deaminase Inhibitors; D003839:Deoxyadenosines; D015649:Pentostatin; D009700:Nucleoside Deaminases