INTERLEUKIN-7 (IL-7) ENHANCES CLASS SWITCHING TO IGE AND IGG4 IN THE PRESENCE OF T-CELLS VIA IL-9 AND SCD23

Interleukin-7 (IL-7) is a B-cell growth factor produced by both bone m arrow stroma cells and follicular dendritic cells (FDCs) located in pr imary lymphoid follicles and germinal centers. In this study, we have evaluated the role of IL-7 on human Ig class switching. IL-7 was added to peripheral blood mononuclear cells (PBMCs) or tonsillar B cells in the absence or presence of IL-4 and/or anti-CD40 monoclonal antibody (MoAb). Alone, IL-7 did not affect Ig production by PBMCs or by anti-C D40 MoAb-stimulated B cells. Rather, IL-7 potentiated IL-4-induced IgE and IgG4 production by PBMCs. In parallel, IgG3 production was also e nhanced but to a lesser extent, whereas the production of the other is otypes was unaltered. The activity of IL-2, IL-9, or IL-15, which shar e usage of the common gamma chain for signaling, was also assessed. IL -9, like IL-7, potentiated mainly IgE and lgG4 production by IL-4-stim ulated PBMCs. IL-15, in contrast, was ineffective, whereas IL-2 enhanc ed the production of all isotypes. More precisely, IL-7 potentiation o f IgE and lgG4 production required the presence of T cells and was acc ompanied by an increase of the expression of two soluble molecules fav oring preferentially IgE and lgG4 synthesis: CD23 (sCD23) and IL-9. Mo reover, neutralizing anti-CD23 and anti-IL-9 antibodies partly inhibit ed the increase of IgE synthesis induced by IL-7. Thus, IL-7 produced locally in the germinal centers by FDCs may interact with T cells and potentiate human IgE and IgG4 switching by favoring IL-9 and sCD23 pro duction. (C) 1998 by The American Society of Hematology.