QUANTITATICN OF LYMPHOCYTE IMMUNOGLOBULIN BIOSYNTHESIS

Abstract

Quantitaticn of peripheral blood lymphocyte immunoglobulin biosynthesis was evaluated as a method for detection of humoral immunodeficiency. Lymphocytes isolated from 3-15 cc of heparinized blood, using Ficoll-Hypaque gradients, were incubated in leucine free medium (1×106 cells/cc) with tritiated leucine for 48 and 72 hrs. Newly synthesized secreted IgG and total immunoalobulins were measured using specific anti-immunoglobulin antibodies coupled to insoluble bromacetylcellulose. Synthesis was readily detected in newborn infants as young as 28 wks gestation. The normal range (6 individuals) for total immunoglobulin synthesis and IgG synthesis was 1.3-5.5%, and 0.3-1.6%, respectively, of total secreted proteins. The lymphocytes of a patient with X-linked agammaglobulinemia synthesized no immunoglobulins. In a patient with non-X-linked agammaglobulinemia (with B-cells), total immunoglobulin and IgG synthesis was 0.20% and 0.13%, respectively. A patient with common variable hypogammaglobulinemia (normal IgM, low IgG, absent IgA) also showed depressed synthesis (total immunoglobulins 0.70%, IgG 0.40%). Quantitation of lymphocyte immunoglobulin biosynthesis appears to be a useful technique for the early diagnosis of humoral immunodeficiency and may be of potential value for the detection of immunodeficiency disease carriers.