Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells.

Abstract

Recently the cDNA encoding interleukin 13 (IL-13), a T-cell-derived cytokine, was cloned and expressed. The present study demonstrates that IL-13 induces IgG4 and IgE synthesis by human B cells. IL-13-induced IgG4 and IgE synthesis by unfractionated peripheral blood mononuclear cells and highly purified B cells cultured in the presence of activated CD4+ T cells or their membranes. IL-13-induced IgG4 and IgE synthesis is IL-4-independent, since it was not affected by neutralizing anti-IL-4 monoclonal antibody. Highly purified, surface IgD+ B cells could also be induced to produce IgG4 and IgE by IL-13, indicating that the production of these isotypes reflected IgG4 and IgE switching and not a selective outgrowth of committed B cells. IL-4 and IL-13 added together at optimal concentrations had no additive or synergistic effect, suggesting that common signaling pathways may be involved. This notion is supported by the observation that IL-13, like IL-4, induced CD23 expression on B cells and enhanced CD72, surface IgM, and class II major histocompatibility complex antigen expression. In addition, like IL-4, IL-13 induced germ-line IgE heavy-chain gene transcription in highly purified B cells. Collectively, our data indicate that IL-13 is another T-cellderived cytokine that, in addition to IL-4, efficiently directs naive human B cells to switch to IgG4 and IgE production.

IL‐18 stimulates IL‐13‐mediated IFN‐γ‐sensitive host resistance in vivo

“…-1198 Immunity to infection IL-13, originally described as a T cell-derived antiinflammatory cytokine, has multiple biological activities. Like IL-4, IL-13 up-regulates CD23, CD71 and MHC class II expression on B cells and monocytes [32], elicits B cell proliferation and induces IgG4 and IgE production by human B cells [32], and promotes Th2 cell differentiation [33]. In addition, IL-13 plays a dominant role to IL-4 in mediating worm expulsion to Nippostrongylus brasiliensis [34], exerts protective functions both in the chronic stages of some Leishmaniasis major infections [35] and in Listeria monocytogenes infection in the context of a Th1 cytokine response [36], and acts as the key mediator in the pathogenesis of allergic asthma [37].…”

IL‐4 Synergizes with IL‐10 and Anti‐CD40 MoAbs to Induce B‐Cell Differentiation in Patients with Common Variable Immunodeficiency

“…IL-13 has been shown to share many of its biological activities with IL-4, although IL-13, in contrast to IL-4, does not act on human T cells [48]. Like IL-4, IL-13 induces CD23 expression on B cells, directs Ig isotype switching to IgG4 and IgE synthesis, and inhibits production of pro-inflammatory cytokines by monocytes [49,50]. However, the observation that IL-13 was less efficient in inducing B-cell differentiation than IL-4 is consistent with earlier results indicating that IL-13 is less potent than IL-4 in inducing IgE synthesis by normal human B cells [49], or immature fetal B cells [51].…”

“…Like IL-4, IL-13 induces CD23 expression on B cells, directs Ig isotype switching to IgG4 and IgE synthesis, and inhibits production of pro-inflammatory cytokines by monocytes [49,50]. However, the observation that IL-13 was less efficient in inducing B-cell differentiation than IL-4 is consistent with earlier results indicating that IL-13 is less potent than IL-4 in inducing IgE synthesis by normal human B cells [49], or immature fetal B cells [51]. However, like IL-4, IL-13 might be useful in the treatment of some patients with defective humoral immunity, such as in SCID patients, who have mutations in their gene encoding the common g-chain, a component of receptors for IL-2, IL-4, IL-7, IL-9 and IL-15 [52][53][54].…”

Cytokine Gene Polymorphism in Idiopathic Nephrotic Syndrome Children

“…Stimuli, such as allergens, may activate common immune mechanisms, which subsequently result in proteinuria in children with MCNS. Several investigators have demonstrated the potential role of Th2 cytokines in this disease [3][4][5][6].…”