Interleukin-7 (IL-7) Enhances Class Switching to IgE and IgG4 in
the Presence of T Cells Via IL-9 and sCD23
Pascale Jeannin,
Yves Delneste,
Sybille Lecoanet-Henchoz,
Denise Gretener, and
Jean-Yves Bonnefoy
From the Geneva Biomedical Research Institute, Immunology Department,
Glaxo Wellcome Research and Development SA, Geneva, Switzerland.
Interleukin-7 (IL-7) is a B-cell growth factor produced by both bone
marrow stroma cells and follicular dendritic cells (FDCs) located in
primary 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-CD40 MoAb-stimulated B cells. Rather, IL-7 potentiated
IL-4-induced IgE and IgG4 production by PBMCs. In parallel, IgG3
production was also enhanced but to a lesser extent, whereas the
production of the other isotypes was unaltered. The activity of IL-2,
IL-9, or IL-15, which share usage of the common
chain for
signaling, was also assessed. IL-9, like IL-7, potentiated mainly IgE
and IgG4 production by IL-4-stimulated PBMCs. IL-15, in contrast, was
ineffective, whereas IL-2 enhanced the production of all isotypes. More
precisely, IL-7 potentiation of IgE and IgG4 production required the
presence of T cells and was accompanied by an increase of the
expression of two soluble molecules favoring preferentially IgE and
IgG4 synthesis: CD23 (sCD23) and IL-9. Moreover, neutralizing anti-CD23 and anti-IL-9 antibodies partly inhibited 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 production.
Blood, Vol. 91 No. 4 (February 15), 1998:
pp. 1355-1361
© 1998 by The American Society of Hematology.