EFFECTS OF INTERFERON-ALPHA AND INTERFERON-GAMMA ON B-CELL DIFFERENTIATION IN MACROGLOBULINEMIA

We previously showed that clonal blood B cells from patients with macr oglobulinemia spontaneously differentiate in vitro to plasma cells via an IL-6 autocrine pathway. Here we investigate whether interferon-alp ha or -gamma would interfere with B cell differentiation either in pat ients with IgM gammopathy of undetermined significance (IgM-MGUS) or W aldenstrom's macroglobulinemia (WM). A 65% inhibition of in vitro B ce ll differentiation was noted in 8 of 10 patients in the presence of ei ther interferon -alpha or -gamma. Cells from 4 patients (3 IgM-MGUS an d 1 WM) were susceptible to both types of interferon while B cell diff erentiation from 4 patients (3 IgM-MGUS and 1 WM) was inhibited only b y one type of interferon. During in vitro culture, IL6 synthesis was u naffected by the presence of interferon alpha or gamma in the 8 cases studied. Likewise, no modulation of the constitutive B cell IL6-R expr ession from 6 patients studied (4 WM and 2 IgM-MGUS) was observed. The se data indicate that interferons did not modify the differentiation o f 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 expr ession.