Regulation by interferon α of immunoglobulin isotype selection and lymphokine production in mice

Abstract

Antigens and infectious agents that stimulate interferon α(IFN-α) production in mice induce antibody responses that are predominantly of the immunoglobulin (Ig)G2a isotype and contain little or no IgE. This suggested the possibility that IFN-α might have a role in directing Ig isotype selection. Consistent with this possibility, we have found that injection of mice with recombinant mouse IFN-α suppresses IgE secretion, enhances IgG2a secretion, and has no independent effect on IgG1 secretion in mice stimulated with a foreign anti-IgD antibody. Injection of mice with polyinosinic acid-polycytidylic acid (poly I·C), an inducer of macrophage IFN-α production, also suppresses the anti-IgD antibody-induced IgE response and stimulates the IgG2a response; these effects are blocked by a sheep antibody that neutralizes mouse IFN-α/β. Both recombinant IFN-α and poly I·C have maximum IgE suppressive and IgG2a stimulatory effects when injected early in the anti-IgD antibody-induced immune response. Addition of IFN-α to mouse B cells cultured with lipopolysaccharide (LPS) + interleukin 4(IL-4) suppresses both IgG1 and IgE production, but much less potently than IFN-γ. IFN-α suppresses anti-IgD antibody-induced increases in the level of splenic IL-4 mRNA, but enhances the anti-IgD antibody-induced increase in the splenic level of IFN-γ mRNA. These results are consistent with the effect of IFN-α on Ig isotype expression in mice, as IL-4 stimulates IgE and suppresses IgG2a secretion while IFN-γ exerts opposite effects. These observations suggest that antigen presenting cells, by secreting IFN-α early in the course of an immune response, can influence the nature of that response both through direct effects on B cells and by influencing the differentiation of T cells.