Open Access

VIEWPOINT

Crosslinking-mediated activation of the FcεRI: Does it need antigen for success?

by MICHAEL HUBER^*, SANDRO CAPELLMANN

Institute of Biochemistry and Molecular Immunology, Medical Faculty, RWTH Aachen University, Aachen, 52074, Germany

* Address correspondence to: Michael Huber,

BIOCELL 2022, 46(5), 1125-1129. https://doi.org/10.32604/biocell.2022.018513

Received 30 July 2021; Accepted 08 October 2021; Issue published 06 January 2022

Abstract

Mast cells (MCs), hematopoietic cells of the myeloid lineage, are well-known for their pro-inflammatory nature contributing to the development of various allergic and autoimmune diseases. One of the characteristic receptors on MCs, the high-affinity receptor for IgE (FcεRI), is activated in its IgE-bound state via binding and crosslinking by polyvalent antigen. This results in its phosphorylation by the SRC family kinase LYN, initiating differential signaling pathways, eventually triggering immunological effector functions, such as degranulation and cytokine production. Few publications have reported on FcεRI-dependent but antigen-independent MC activation by antibody-mediated crosslinking of membrane molecules (e.g., transmembrane proteins and glycosphingolipids) that are both localized in membrane rafts and in close vicinity to the FcεRI. In this Viewpoint we will briefly introduce FcεRI-mediated MC stimulation, cite examples of FcεRI-proximal molecules, the crosslinking of which can cause FcεRI-dependent MC activation, and discuss the potential of certain viruses as well as auto-antibodies to act as indirect FcεRI-crosslinking agents. In latter cases, antigen-independent FcεRI-mediated pro-inflammatory MC activation could contribute to the development of detrimental cytokine storms.

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