Effects of interferon-alpha and -gamma on B cell differentiation in macroglobulinemia

We previously showed that clonal blood B cells from patients with macroglobulinemia spontaneously differentiate in vitro to plasma cells via an IL-6 autocrine pathway. Here we investigate whether interferon-alpha or -gamma would interfere with B cell differentiation either in patients with IgM gammopathy of undetermined significance (IgM-MGUS) or Waldenström's macroglobulinemia (WM). A 65% inhibition of in vitro B cell differentiation was noted in 8 of 10 patients in the presence of either interferon-alpha or -gamma. Cells from 4 patients (3 IgM-MGUS and 1 WM) were susceptible to both types of interferon while B cell differentiation from 4 patients (3 IgM-MGUS and 1 WM) was inhibited only by one type of interferon. During in vitro culture, IL6 synthesis was unaffected by the presence of interferon alpha or gamma in the 8 cases studied. Likewise, no modulation of the constitutive B cell IL6-R expression from 6 patients studied (4 WM and 2 IgM-MGUS) was observed. These data indicate that interferons did not modify the differentiation of B cells in macroglobulinemia via modulation of the IL6-IL6-R pathway. This is in contrast with the mode of action of interferons in other lymphoid malignancies such as multiple myeloma or chronic lymphocytic leukemia where they directly modulate IL6-production and/or IL6-R expression.