IL-4 and IL-10 suppress viral-specific antibody responses by memory B cells

Memory B cells can be reactivated in vitro by specific antigens in the presence of T helper cells or T cell-derived soluble factors, such as IL-2. Moreover IL-4 and IL-10 have been shown to be important factors for B cell growth and differentiation. The synergistic induction of Ig secretion by IL-2, in the presence of IL-4 and IL-10, has been previously reported using polyclonal B cell activators. To investigate the role of these cytokines in antigen-specific antibody response, highly purified tonsillar B lymphocytes were cultured in vitro for ten days with different combinations of purified respiratory syncytial virus (RSV) antigen, rhIL-2, rhIL-4 and rhIL-10. Although the combination of IL-2 (20 U/ml) and IL-10 (100 ng/ml) or IL-4 (100 U/ml) was found to stimulate polyclonal IgG, IgM and IgA response, the levels of specific IgG, IgM and IgA in absence of RSV remained below the threshold of detection, regardless of which cytokines were used for stimulation. Addition of RSV and IL-2 to the culture medium resulted in secretion of anti-RSV IgG Ab (564±86 EU/ml), but not IgM or IgA. When IL-4 or IL-10 were included in the culture, a significant inhibition of RSV-specific IgG Ab was observed. On the other hand, the total IgG, IgM and IgA secretion was not significantly altered by the presence of IL-4 and IL-10. These results show that IL-2, in the absence of co-stimulatory molecules such as CD40, can efficiently drive specific antigen-activated memory B cells to antibody secreting cells. A novel inhibitory effect of IL-4 and IL-10 on viral-specific Ab production is suggested.