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.