Immunoglobulin E (IgE) is central to the induction of allergic diseases through its binding to the high-affinity receptor (Fc epsilon R1) on mast cells and basophils. Crosslinking by allergens of the bound IgE leads to the release of various inflammatory mediators. IgE production by B cells requires a physical interaction with T cells, involving a number of surface adhesion molecules, as well as the soluble factors interleukin-4 (IL-4) and IL-13 (ref. 5) produced by T cells, basophils and mast cells. Here we report that, in the presence of IL-4, mast and basophilic cell lines can provide the cell contact signals that are required for IgE synthesis. The human cell lines HMC-1 (mast) and KU812 (basophilic) both express the ligand for CD40 (CD40L) which is shown to be responsible for the IgE production. Moreover, freshly isolated purified human lung mast cells and blood basophils are also shown to express CD40L and to induce IgE production. This evidence suggests that mast cells and basophils may therefore play a key role in allergy not only by producing inflammatory mediators, but also by directly regulating IgE production independently of T cells.

CD40 ligand (CD40L), a surface molecule which can be expressed by T cells, mast cells and basophils, has been shown to be involved in the control of B cell proliferation, immunoglobulin class switching as well as in the activation of monocytes and T cells. We demonstrate that CD40L can also be expressed constitutively by eosinophils from an hypereosinophilic patient or, upon activation, by the eosinophilic cell line EOL-3 and normal blood eosinophils. Eosinophils were able to induce, in conjunction with IL-4, CD40L-dependent B cell proliferation in vitro. These results suggest that CD40L could play a role in the inflammatory processes during which eosinophil infiltration and activation are observed.

Germinal center cells (GCC) are programmed to die by apoptosis unless they receive a positive signal for rescue. The primary signal in vivo is believed to be dependent on interaction with antigen held as immune complexes on follicular dendritic cells (FDC), a subset of which express large amounts of CD23, a low-affinity receptor for IgE. Recombinant soluble CD23 (sCD23) and interleukin-1 have been found to potentiate the survival of GCC in vitro. Recently, CD23 was shown to interact specifically with a ligand other than IgE, namely CD21 (CR2/Epstein-Barr virus receptor). In the present study, we show that a subset of anti-CD21 monoclonal antibodies behave similarly to soluble CD23 in their effect on GCC inasmuch as they: (i) diminish the occurrence of apoptosis; (ii) promote a plasmacytoid appearance in rescued cells; (iii) up-regulate expression of the Bcl-2 proto-oncogene. These findings indicate that FDC-derived CD23 exerts its effects on GCC via CD21.

Recombinant full-length human CD23 incorporated into fluorescent liposomes was used to detect a ligand for CD23 on the basophilic leukemia cell line, KU 812. Based on our recent finding that CD23 interacts with CD21 on subsets of B and T cells, we investigated if the same ligand was involved on KU 812 cells. An anti-CD21 monoclonal antibody (mAb) BU-33, was able to totally block CD23-liposome binding to KU 812 cells. Moreover, KU 812 cells express CD21 mRNA and have a cell surface molecule that reacts with anti-CD21 mAb. The CD23/CD21 interaction was not merely physical but was also associated with an increase in histamine release by KU 812 cells. Both recombinant soluble CD23 and an anti-CD21 mAb-mediated effect on histamine release was not restricted to and anti-CD21 mAb-mediated effect on histamine release was not restricted to the leukemic cell line, but was also observed with normal human blood basophils. These data demonstrate that CD21 is expressed on basophilic cells and that CD21 controls histamine production upon ligand-induced stimulation (CD23 or anti-CD21 mAb).

No abstract