Functional assessment of a B cell defect in patients with selective IgA deficiency.

The cellular basis of selective IgA deficiency was investigated by examining the terminal differentiation of B lymphocytes co-cultured with varying ratios of T lymphocytes in the presence of pokeweed mitogen. Eight patients were studied who had serum IgA concentrations <0·05 mg/ml, salivary IgA <0·01 mg/ml, and between 0·8 and 4% lymphocytes with surface IgA markers. Peripheral blood lymphocytes from patients and normal donors were separated into B cell (non T cell) and T cell fractions by E-rosetting. Microcultures were established at eleven B cell to T cell ratios from 100% B cells to 100% T cells. After 7 days, immunoglobulin in the supernatant fluid was measured by radioimmunoassay. Cultures containing patients' B cells and either autologous or allogeneic T cells produced very low or undetectable amounts of IgA. However, cultures from six out of eight patients contained cells with intracytoplasmic IgA. Secretion of IgM by the patients' B cells was identical to that of normal donors. Surprisingly, IgG production by patients' B cells was less than that produced by normal B cells especially in the mid-range ratios of the microcultures. Production of IgA, IgG and IgM by normal B cells from peripheral blood or tonsils was very similar in the presence of normal T cells or patients' T cells. In cultures containing optimal ratios of normal B cells, the patients' T cells not only did not suppress IgA production but also gave normal help for IgA production. It was concluded, on the basis of these studies, that a defect in patients with selective IgA deficiency was the functional inability of their B cells to produce normal amounts of IgA even when provided with normal allogeneic T cell help.