Immunoglobulin Superantigen Protein L Induces IL-4 and IL-13 Secretion from Human FcεRI+ Cells Through Interaction with the κ Light Chains of IgE

Abstract

Peptostreptococcus magnus protein L is a multidomain bacterial surface protein that correlates with virulence. It consists of up to five homologous Ig-binding domains (B1–B5) that interact with the variable domain of Ig κ L chains. Intact protein L stimulates the synthesis and the release of IL-4 and IL-13 from human basophils in vitro. A protein L fragment covering the Ig-binding domains B1–B4 also induced IL-4 and IL-13 release from basophils. There was an excellent correlation (rs = 0.82; p < 0.001) between the maximal percent IL-4 release induced by protein L and that induced by anti-IgE and between intact protein L and the B1–B4 fragment (rs = 0.90; p < 0.01). Removal of IgE bound to basophils markedly reduced the IL-4 release induced by anti-IgE, protein L, and B1–B4. Preincubation of basophils with protein L or anti-IgE caused complete cross-desensitization to subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (λ chains) blocked anti-IgE-induced IL-4 release, but not the releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (κ chains) blocked both anti-IgE- and protein L-induced secretion. Cyclosporin A, but not cyclosporin H, inhibited protein L-induced release of IL-4 and IL-13 from basophils. Thus, protein L acts as a bacterial Ig superantigen to induce the synthesis and release of IL-4 and IL-13 from basophils by interacting with κ L chains of the IgE isotype.

Bacterial Surface Protein L Binds and Inactivates Neutrophil Proteins S100A8/A9

“…Although most of the protein L is bound to the bacterial surface, some is also released into the medium during growth (4,5). As mentioned, protein L, by cross-linking cell-bound IgE, can induce a powerful inflammatory response (14,15). The rationale for a member of the normal flora to induce inflammation is not obvious, but there could be nutritional-ecological reasons.…”

“…Protein L preferentially binds Ig L chains of the type through interactions with the variable domain, but without interfering with the Ag binding site (9 -12). The molecule contains multiple homologous Ig binding domains, called B repeats (13), and it activates human basophils and mast cells by cross-linking surface-associated IgE, resulting in the release of proinflammatory mediators (14,15). These different observations indicate that the presence of protein L at the surface of F. magna enhances the potential pathogenicity of the bacteria.…”

The immune network in thyroid cancer

“…Primary sources of IL-4 include human Th2 cells, basophils and T follicular helper cells (Tfh). 11,12 Exposure to IL-4 or IL-13 induces alternative (M2) activation of macrophages and tumor-associated macrophages (TAMs) in TC displayed an M2-like phenotype. 13,14 Recently, a link between ionizing radiation (IR), IL-13 and oxydative stress-induced DNA damage in thyreocytes has been observed.…”

In Vivo VL-Targeted Activation-Induced Apoptotic Supraclonal Deletion by a Microbial B Cell Toxin

“…Before we performed these studies, the only available reports on the cellular interactions of PpL had been limited to binding studies on naive mononuclear cells (24), and in vitro assays demonstrating that PpL (like SpA) is capable of triggering mast cells and basophils via their membrane-bound Ig (32). In fact, we were uncertain whether PpL was capable of deleting B cells, as we were concerned that PpL might not induce a suitable BCR signal due to subtle differences in affinity or avidity, or perhaps because affected B cells might have the potential capacity to recruit additional second signals.…”