IgG subclasses determine pathways of anaphylaxis in mice

Area of Science:

• Immunology
• Allergy Research
• Fc Receptor Signaling

Background:

• Allergen-specific IgG induces systemic anaphylaxis through IgG Fc receptors (FcγRs).
• Mouse IgG subclasses (IgG1, IgG2a, IgG2b) exhibit distinct FcγR binding affinities and mediate anaphylaxis.
• Understanding these interactions is crucial for deciphering allergic responses.

Purpose of the Study:

• To elucidate the specific pathways governing IgG1, IgG2a, and IgG2b-dependent passive systemic anaphylaxis.
• To identify the roles of different FcγRs and cellular components in these anaphylactic models.

Main Methods:

• Induction of systemic anaphylaxis in mice using specific IgG subclasses (IgG1, IgG2a, IgG2b) and a model antigen.
• Evaluation of anaphylaxis severity by monitoring rectal temperature.
• Assessment of FcγR-deficient mice, mediator antagonists, and depletion of specific immune cells (basophils, monocytes/macrophages, neutrophils).
• Analysis of FcγR expression on immune cells before and after anaphylaxis.

Main Results:

• Activating FcγRIII was identified as the primary receptor mediating all three IgG subclass-induced anaphylaxis models.
• Subsequent downregulation of FcγRIII was observed post-anaphylaxis.
• Differential reliance on histamine release and contributions from mast cells, basophils, macrophages, and neutrophils were noted.
• Basophil involvement and histamine predominance in IgG1 and IgG2b-induced anaphylaxis correlated with negative regulation by inhibitory FcγRIIB.

Conclusions:

• Differential expression of inhibitory FcγRIIB on myeloid cells and its varying affinity for IgG subclasses dictate the roles of different immune cells in anaphylaxis.
• These findings reveal intricate regulatory mechanisms of IgG-dependent reactions involving multiple cell populations.
• The study highlights novel complexities in the cellular involvement and regulation of IgG-mediated anaphylaxis in vivo.