Phenotypic heterogeneity in X-linked infantile agammaglobulinemia with in vitro monocyte suppression of immunoglobulin synthesis

Abstract

In vitro immunoglobulin (Ig) production was studied in two brothers with X-linked infantile agammaglobulinemia (XLA) to determine the etiology of their differing serum Ig levels. Patient 1 (P1), age 17 years, had an IgG level of 122 mg/dl, IgA undetectable, and IgM levels of 0 to 6 mg/dl while patient 2 (P2), age 14 years, had IgG level of 184 mg/dl, IgA undetectable, and IgM values of 24 to 35 mg/dl. Both boys had normal percentages of T lymphocytes and normal responses to PHA. P1 had 1% circulating B cells and P2 had no detectable circulating B cells. Both boys had identical HLA-A and HLA-B antigens and similar complete blood counts and differentials, including 8–18% monocytes. In vitro Ig synthesis was measured in pokeweed mitogen stimulated cell cultures by [ 35S]methionine incorporation and Ig immunoprecipitation. Neither boy was able to synthesize Ig in vitro, but only P1 had cells which suppressed Ig synthesis of control cells. T-Cell fractions from these boys showed normal helper and suppressor activity when cultured with control B cells. However, the non-T-cell fraction from P1 suppressed Ig synthesis. This suppressor effect could be eliminated by removing plastic adherent cells from P1's mononuclear cells or T-depleted fraction, suggesting monocyte suppressor cells. We conclude that the B-cell defect in XLA can be modified by secondary monocyte-mediated suppression, resulting in phenotypic variation in laboratory findings.