Lymphocyte subpopulations in X-linked severe combined immunodeficiency (SCID): Evidence against a stem cell defect. Transformation response to calcium lonophore A23187

Abstract

Lymphocytes from a patient with severe combined immunodeficiency (SCID) of the X-linked adenosine deaminase-positive type were studied in detail. Eighty per cent of peripheral blood cells were positive for surface immunoglobulins, the predominant fluorescence being immunoglobulin G (IgG). Double-labeling experiments showed 30 per cent of cells to be positive for γ and μ; all μ-staining cells also had γ. Few δ-positive cells were found. Both the γ- and μ-bearing cells contained either κ and λ light chains, the ratio of κ to λ being 4:1. These high percentages of immunoglobulin-bearing cells are in contrast to the very low or absent serum immunoglobulin concentrations and suggest failure of differentiation into actively-secreting lymphocytes or plasma cells. No evidence for circulating suppressor cells was found. An unusual subpopulation of B cells, previously termed B 2, predominated in that complement receptors C3b and C3d were absent by EAC and Raji technics. Thymus-derived lymphocytes were absent in this patient, and T-cell functions were severely impaired as measured by skin test anergy, and mitogen and allogeneic responses in vitro. An increased tridiated thymidine ( 3H-TdR) incorporation and a normal percentage of cells entering interploid S phase and tetraploid G 2 and M phase of the cell cycle (S-G2-M) (by cytofluorographic analysis) followed the incubation of lymphocytes with calcium ionophore A23187. These membrane findings suggest possible pathogenetic mechanisms for the deficiencies in patients with this specific subset of SCID disease. The absence of a putative endogenous membrane ionophore, a defect in cytoskeleton, for example, a defect in microtubules or microfilaments, or impaired intracellular cyclic nucleotide activation or distribution, or defects in protein phosphorylation or sialation could all explain these observations.