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Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses

Abstract

Immunoglobulin (Ig)-free light chains IgLC are present in serum and their production is augmented under pathological conditions such as multiple sclerosis, rheumatoid arthritis and neurological disorders. Until now, no (patho)physiological function has been ascribed to circulating Ig light chains. Here we show that IgLCs can confer mast cell–dependent hypersensitivity in mice. Antigenic stimulation results in plasma extravasation, cutaneous swelling and mast-cell degranulation. We show that IgLCs have a crucial role in development of contact sensitivity, which could be completely prevented by a novel IgLC antagonist. Although IgE and IgG1 are central to the induction of immediate hypersensitivity reactions, our results show that IgLCs have similar activity. IgLCs may therefore be a novel factor in the humoral immune response to antigen exposure. Our findings open new avenues in investigating the pathogenesis of autoimmune diseases and their treatments.

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Figure 1: IgLC transfers hapten sensitivity.
Figure 2: Antigen-specificity of sensitization with IgLC.
Figure 3: Mast-cell dependency of hapten-induced ear swelling in IgLC-sensitized mice.
Figure 4: Binding of Ig free light chain to mast cells.
Figure 5: Antigen-specific IgLC is produced after contact sensitization with low molecular weight compounds.
Figure 6: F991 prevents hapten–induced ear swelling in passively and actively sensitized mice.

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Acknowledgements

We thank C. Beukelman for his initial help with the high performance gel filtration experiments; C. Vallinga, D. Kegler, P. van Schaaik, S. de Jager, A. van Houwelingen and B. Blokhuis for expert technical assistance; C. Burger for performing the electron microscopy studies; C. Milstein for providing the oxazolone-specific antibody producing hybridoma; H. Metzger and N. Bloksma for helpful suggestions and critical reading of the manuscript; A. Dvorak for evaluation and discussion of the electron microscopical studies. This work was supported by grants from the Royal Dutch Academy of Arts and Sciences, GlaxoSmithKline, the Netherlands and Fornix Biosciences, the Netherlands.

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Correspondence to Frank A. Redegeld.

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This research is being sponsored in part by Fornix Biosciences, Lelystad, the Netherlands.

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Redegeld, F., van der Heijden, M., Kool, M. et al. Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses. Nat Med 8, 694–701 (2002). https://doi.org/10.1038/nm722

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