Differential regulation of IgG1 and IgE synthesis by interleukin 4.

Abstract

IL-4/B cell stimulatory factor-1 is a T cell-derived lymphokine that has been shown to enhance IgG1 and IgE and to suppress IgG3 and IgG2b secretion by B cells stimulated with bacterial LPS. We show here that the stimulation of IgG1 and IgE secretion in response to rIL-4 is differentially regulated. The dose-response curve for IgG1 production is bimodal with peaks at 100 and 10,000 U/ml. IgE production is modest at 100 U/ml and exhibits a progressive enhancement as the IL-4 concentration is increased to 10,000 U/ml, reaching approximately 1 microgram of IgE from an initial cell number of 2 X 10(4). Both of these effects are reversed by monoclonal anti-IL-4 antibody. Neither the enhancing nor suppressing effects of IL-4 can be explained by changes in viable cell yields or [3H]thymidine incorporation. The production of both IgG1 and IgE is controlled by IL-4 in a two-phase manner. During the initial 2 d of culture with LPS, IL-4 action for both IgG1 and IgE production is relatively concentration independent at doses greater than 600 U/ml. This 2-d treatment leads to maximal IgG1 production at day 6 with no further addition of IL-4. Addition of IL-4 during the final 4 d of culture has no effect at concentrations under 100 U/ml. At higher concentrations, IL-4 is strikingly suppressive for IgG1 production. By contrast, little IgE is produced unless IL-4 is present after 2 d of culture and the response is directly dependent on the concentration of IL-4 during this second phase of culture with maximal responses observed at 10,000 U/ml. These differences in IL-4 requirements for IgG1 and IgE production, respectively, may have an important role in the regulation of the synthesis of these isotypes in responses to microbial antigens.

RANTES Potentiates Antigen-Specific Mucosal Immune Responses

“…These results were surprising since nasal immunization regimen that use soluble protein Ag often result in higher IgG1 Ag-specific Ab titers (35,36). IL-4 supports IgG1 and IgE Ab production and generation; hence, the low levels of anti-OVA IgG1 and IgE Abs were consistent with the observed cytokine profiles (i.e., IL-2, IFN-␥, IL-5, and IL-6) of the OVA-restimulated CD4 ϩ T cells of RANTES-treated mice (37)(38)(39). IFN-␥ production is often associated with IgG2a and IgG3 Ab production (40) and may account for the RANTES-mediated anti-OVA IgG2a and IgG3 Ab responses.…”

Th1 and Type 1 Cytotoxic T Cells Dominate Responses in T-bet Overexpression Transgenic Mice That Develop Contact Dermatitis

“…Because serum cytokines were below the level of detection, we analyzed serum Ig isotypes. IFN-␥ promotes IgG2a class switching while IL-4 promotes IgG1 class switching, so concentrations of serum IgG2a and IgG1 reflect Th1 and Th2 responses in vivo (22)(23)(24). The higher IgG2a/IgG1 ratio present in the sera of Tg mice suggests that T-bet overexpression promotes IgG2a class switching and represses IgG1 class switching.…”

Exacerbated Th2‐mediated airway inflammation and hyperresponsiveness in autoimmune diabetes‐prone NOD mice: a critical role for CD1d‐dependent NKT cells

“…To investigate the peripheral immune response in immunized and challenged mice, we measured serum levels of OVA-specific IgE, the production of which depends on both IL-4 and IL-13 in this model [18,22,23]. Fig.…”