Profile of multiple lymphocyte functional defects in acquired hypogrammaglobulinemia, derived from in vitro cell recombination analysis.

Immunoregulatory defects in patients can be assigned to B cells, T helper cells, or T suppressor cells by means of a modification of the in vitro PWM-stimulated Ig biosynthesis assay. When lymphocyte subpopulations from patient and normal are recombined, multiple internal comparisons within a single experiment reveal the functional activity of each subpopulation. By this technique we studied nine adult patients with acquired panhypogammaglobulinemia and one with isolated IgG deficiency. Low total Ig production by the B cell fraction was demonstrated in seven of the nine panhypogammaglobulinemic patients. In four of these seven, IgG and IgA secretion was markedly reduced compared with IgM. In the two patients with normal total Ig production, elevated IgM compensated for lower IgA and IgG. The one patient with no surface Ig+ cells had a B cell defect, but no T cell defect. Reduced T help and excessive T suppression characterized two of the four patients with the most severe B cell defects. Three patients were anergic by delayed hypersensitivity skin testing and failed to sensitize to DNCB, but the patient with the most severe T cell defects in vitro was not among them. One of these three patients showed a mild T cell help defect and suppressor excess and the other two had pure B cell defects. Thus, anergy and T regulator function were not correlated. In three instances where hypersuppression was more evident by adding patient unfractionated cells than by adding patient T cells, suppression by the T depleted fraction could be demonstrated. No cases of radiation-resistant T suppression were revealed among the seven patients tested. Subnormal total protein synthesis, noted in six of seven patients with low Ig production, was invariably less marked than the Ig defect and often affected both T and B cells. One additional patient with pure IgG deficiency of 2 yr duration was essentially normal in her in vitro lymphocyte function. The general applicability of this experimental design for analysis of positive or negative immunoregulatory abnormalities is emphasized.