Immunoglobulin heavy constant gamma 4 (IGHG4) (IgG4)

B cells producing allergen-specific IgG4 are a specialized subset of B lymphocytes characterized by the expression of the IgG4 isotype of the B-cell receptor. In the context of allergic diseases, these cells are considered protective as they produce allergen-specific IgG4 antibodies that function as blocking antibodies, competing with IgE for allergen binding and thereby inhibiting the activation of mast cells and basophils (Akdis & Akdis, 2014; Aalberse et al., 2009). The induction of these cells is a primary mechanism and biomarker of successful allergen-specific immunotherapy (AIT) for conditions such as allergic rhinitis and venom hypersensitivity (Jutel et al., 2015). Conversely, in IgG4-related disease (IgG4-RD), an abnormal expansion of these B cells and their derivative plasma cells leads to systemic fibro-inflammatory lesions in various organs, including the pancreas and salivary glands (Stone et al., 2012). Therapeutic strategies include the use of allergen extracts to deliberately induce these cells for allergy treatment, or the use of B-cell depleting agents like rituximab to reduce their numbers in the treatment of IgG4-RD (Davies et al., 2013). Monitoring the frequency of these cells and the levels of their secreted IgG4 is crucial for assessing the efficacy of immunotherapy and the progression of inflammatory disease.

Other names

IgG4-expressing B cellsAllergen-specific IgG4-producing B cellsIgG4+ B cellsIgG4-positive B cellsRegulatory B cells (subset)

Allergen immunotherapy (AIT) induces the expansion of B cells that produce allergen-specific IgG4 antibodies, which act as blocking antibodies to prevent IgE-mediated mast cell activation. In IgG4-related disease (IgG4-RD), these cells are pathogenic and are targeted for depletion using anti-CD20 or anti-CD19 therapies to reduce fibro-inflammatory tissue damage. Additionally, IL-4/IL-13 inhibitors like dupilumab can prevent the initial class-switching of B cells to the IgG4 isotype.