Suppression of polyclonal and antigen-specific murine IgG1 but not IgE responses by neutralizing interleukin-6 in vivo.
The crucial role of interleukin (IL)-4 in the induction of murine IgG1 and IgE responses, which are coupled through the process of sequential isotype switching, has been well documented. Whereas IL-4 is obligatory for the induction of IgE responses, it enhances IgG1 responses. In this study, using neutralizing antibodies, we provide evidence that, besides IL-4, also IL-6 is required for obtaining peak IgG1 responses. The mRNA levels of these two cytokines are coordinately expressed in the spleen of mice immunized with trinitrophenol-keyhole limpet hemocyanin (TNP-KLH). No IL-6 requirement was observed for peak IgE responses. The IL-6 dependence of IgG1 responses was found for both antigen-specific and polyclonal responses. Moreover, it was noted using TNP-KLH and goat anti-mouse (GAM) IgD as antigen that polyclonal IgG1 responses are more dependent on IL-6 than antigen-specific responses. In vitro experiments revealed that exogenous IL-6 neither enhanced nor inhibited the IgG1 and IgE production by naive B cells, suggesting that IL-6 did not interfere with the IL-4-induced isotype switch potential. Primary and memory IgG1 responses were both similarly dependent on IL-6. These observations point to a role of IL-6 in the terminal differentiation of B cells switched to IgG1. Neutralization of IL-6 did not inhibit either antigen-specific or polyclonal IgE responses. Therefore, it was concluded that IL-6 is not involved in the terminal differentiation of B cells switched to IgE. These findings thus provide a distinct role for IL-6, besides IL-4, in regulating murine IgG1 responses. The formation of IgE, however, is completely dependent on IL-4 alone.
van Ommen
R
R
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Vredendaal
A E
AE
Savelkoul
H F
HF
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D017578:Immunoglobulin Class Switching; D007072:Immunoglobulin D / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D015847:Interleukin-4 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009559:Nippostrongylus / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
D006241:Haptens; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D015850:Interleukin-6; D012333:RNA, Messenger; C054401:trinitrophenyl keyhole limpet hemocyanin; D015847:Interleukin-4; D007073:Immunoglobulin E; D006433:Hemocyanins