Cytokine Regulation Immunoglobulin Isotype Production

Abstract : Immunoglobulin (Ig) isotype switching IS a process whereby B lymphocytes, initially expressing membrane (m)IgM and/or mIgD, switch, upon activation to the expression of one of 4 IgG subclasses (lgG3, IgG I, IgG2b, IgG2a), IgE, or IgA. The Ig class switch confers a new effector function upon the antibody without changing its antigen specificity thus augmenting the biologic diversity of the humoral immune response. Previously, cytokines were shown to induce switching to particular 19 classes in activated murine B cells. Thus, IL-4 stimulated IgG I and IgE switching, IFN-gamma selectively induced IgG2a, and TGF-beta promoted the switch to IgA. Our studies further elucidated the role of cytokines in Ig class switching by: I) identifying the cytokines which functioned as switch factors for IgG3 and IgG2b, 2) establishing the parameters leading to high-rate IgA class switching and, 3) providing additional evidence that the nature of the B cell activator played a determining role in cytokine-directed Ig isotype production.