Defect in IgA secretion and in IgA specific suppressor cells in patients with selective IgA deficiency

The nature of the defect in patients with selective IgA deficiency was investigated using a technique established to study terminal differentiation of B lymphocytes into immunoglobulin synthesizing and secreting cells. The peripheral blood lymphocytes from normal individuals had geometric mean synthetic rates of 4910 ng for IgM, 1625 ng for IgG and 1270 ng for IgA per 2 x 10(6) cells in culture for 7 days in the presence of pokeweed mitogen. The cultured lymphocytes from each of the 14 patients with selective IgA deficiency studied synthesized normal quantities of IgG and IgM but secreted less than 100 ng of IgA into the media. However, 11 of the 14 patients studied synthesized IgA by the 7th day in PWM stimulated cultures as assessed by staining for cytoplasmic IgA using fluorescein-labeled anti-IgA antisera. Synthesis and secretion of IgA by normal cells was not suppressed when they were co-cultured with lymphocytes from these patients that synthesize but do not secrete IgA. Three of the 14 patients did not have lymphocytes with IgA demonstrable in their cytoplasm following culture. When the lymphocytes from these 3 patients were co-cultured with normal lymphocytes and pokeweed mitogen the synthesis of IgA by the normal cells was depressed by 80 to 100%. Synthesis of IgG and IgM was not depressed. These studies suggest that lymphocytes cultured with pokeweed mitogen from the majority of patients with selective IgA deficiency can synthesize IgA but have a defect in IgA secretion. A smaller group of the patients do not synthesize IgA and have IgA specific suppressor cells that prevent B cells from maturing into IgA synthesizing and secreting cells.