Enhanced Antibody Response in the Presence of Partial Adenosine Deaminase Inhibition

Abstract

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 10⁶ 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/10³ 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.