Mast cells are crucial effector cells in allergic reactions, where IgE is the best-known mechanism to trigger their degranulation and the release of allergic mediators. Mast cells are also found activated in inflammatory conditions such as autoimmune diseases, chronic inflammatory conditions in upper and lower airways, intestine and skin, neuroinflammation, and cancer, conditions generally not paralleled with an increased antigen-specific IgE expression. However, mast cells can be activated by numerous other stimuli such as complement factors, toll-like receptor ligands, neuropeptides, cytokines, sphingolipids, ATP/ADP/adenosine, histamine and various exogenous compounds. Previously, we have shown that immunoglobulin free light chains (FLC) may also trigger antigen-specific mast cell activation in the absence of IgE. FLC were shown to be increased in various inflammatory disease such as rheumatoid arthritis, non-allergic rhinitis, COPD, inflammatory bowel disease, and cancer and correlated with disease activity. In various preclinical models, we demonstrated that FLC may be of importance to induce mast cell activation and the onset of an inflammatory response. Interestingly, current experiments indicate that FLC may synergize with IgE to stimulate mast cell degranulation. Under conditions of minimal mast cell stimulation via IgE-receptor crosslinking, co-stimulation with FLC strikingly enhanced mast cell activation. These novel findings suggest that this synergy may be relevant under conditions of low local or systemic IgE production.
Keywords: mast cell, IgE, immunoglobulin free light chain, allergy, inflammatory diseases, cancer

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