In vitro analysis of lymphocyte functions in common variable immunodeficiency: heterogeneity in B-cell defects

Ten patients with common variable immunodeficiency were classified into three groups according to the number of circulating B-cells, i.e. B-cells being absent (three patients), very low (three patients) or within the normal range (four patients). The four patients in the last group showed significant proliferative responses to the T-independent B-cell mitogen, formalin-fixed Staphylococcus aureus, Cowan I. Further study of these patients by co-cultures with allogeneic T or B-cells in various combinations with pokeweed mitogen showed that two patients had an intrinsic B-cell defect without T-cell defect. The third patient had a T-cell dysfunction (i.e. his T-cells could only help the B-cells of some individuals) resulting in a defect in Ig production. The T-cells of the fourth patient showed poor helper function towards all controls. All six patients with absent or very low numbers of B-cells in group I and II had normal T-cell helper function. This study demonstrates that the immunological defect in common variable immunodeficiency is most often a B-cell defect at different stages of their differentiation with sometimes an additional T-cell dysfunction.