Familial macroglobulinaemia: hyperactive B-cells but normal natural killer function.

An Icelandic family with two cases of benign monoclonal gammopathy and one case each of Waldenström's macroglobulinaemia, histiocytic lymphoma and multiple myeloma was first described in 1978. Nine family members had then shown raised values for se-IgM. Of these one has since died and another was not available for testing. In four of the remaining seven se-IgM had returned to normal; the three subjects who still showed raised se-IgM included the case of multiple myeloma diagnosed in 1985. Baseline production of IgM, IgG and Ig in vitro was normal in the 35 family members studied compared with 13 healthy control subjects, but the mean production of all immunoglobulin classes in response to minimal stimulation with PWM (1 microgram/ml) was significantly increased (P < 0.05). Ten family members showed markedly increased production of all three immunoglobulin classes (> 3 x SD above mean for controls). Raised production of IgM never occurred alone, indicating intact class switching. One family member showed extremely high values: IgA: 5.15 micrograms/ml, IgG: 16.3 micrograms/ml, IgM: 24.8 micrograms/ml (means for controls: 0.066, 0.123, 0.185 respectively). These 10 family members were of both sexes, ranged in age from 16 to 84 years and were clustered mainly in three distinct groups within the pedigree suggesting heredity. Proliferative responses to PWM were not significantly increased. Serum levels of interleukin-4 were tested in the patient with multiple myeloma and the family member with highest Ig production and found to be normal. We found no evidence for depressed NK function. Thus, in this family with a tendency for macroglobulinaemia and B cell derived malignancies B cell hyperreactivity was detectable by in vitro testing in several asymptomatic family members, of both sexes and all ages. No evidence was obtained for defects in regulatory mechanisms.