Studies on human lymphocyte 5'-nucleotidase

Abstract

The partial deficiency of 5'-nucleotidase activity found on the circulating mononuclear cells of many patients with 'common variable' or 'X-linked' hypogammaglobulinaemia was not due to abnormal compartmentalisation of the enzyme, altered enzyme kinetics, or the presence of a regulatory factor. Isolation of subpopulations of mononuclear cells from normal adult blood showed that B-lymphocytes, have about four times more 5'-nucleotidase activity per cell than T-lymphocytes, and that monocytes have very little activity. Thus the absence of circulating B-lymphocytes in patients with X-linked hypogammaglobulinaemia contributed to the low activity in these patients, but some patients also had a low level of T-cell 5'-nucleotidase activity. The low enzyme level in 'common variable' hypogammaglobulinaemia was due to one or more of three factors: a low T-cell activity, a reduced percentage of B-cells, and a low activity on the B-celis.

The ability of circulating mononuclear cells to migrate out of capillary tube cultures in vitro was unimpaired, and inhibition of the 5'-nucleotidase activity of normal cells did not affect their migration. Inhibition of the 5'-nucleotidase activity also had no effect on the transformation or immunoglobulin production of tonsil lymphocytes in vitro. However, changes in the enzyme activity on tonsil lymphocytes were observed during cell transformation. Comparison of the 5'-nucleotidase activities of the circulating mononuclear cells from normal adults, cord blood, patients with chronic lymphatic leukemia, and from patients with hypogammagiobulinaemia has led to the hypothesis that the low level of the enzyme on the lymphocytes of patients with 'common variable' and 'X-linked' hypogammaglobulinaemia is not the cause of the disease but reflects a stage of maturation arrest in these cells.