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Review
. 2018 Mar;6(1):13-33.
doi: 10.1002/iid3.192. Epub 2017 Nov 21.

Immunoglobulin G; Structure and Functional Implications of Different Subclass Modifications in Initiation and Resolution of Allergy

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Free PMC article
Review

Immunoglobulin G; Structure and Functional Implications of Different Subclass Modifications in Initiation and Resolution of Allergy

Timothy H Scott-Taylor et al. Immun Inflamm Dis. .
Free PMC article

Abstract

IgE and not IgG is usually associated with allergy. IgE lodged on mast cells in skin or gut and basophils in the blood allows for the prolonged duration of allergy through the persistent expression of high affinity IgE receptors. However, many allergic reactions are not dependent on IgE and are generated in the absence of allergen specific and even total IgE. Instead, IgG plasma cells are involved in induction of, and for much of the pathogenesis of, allergic diseases. The pattern of IgG producing plasma cells in atopic children and the tendency for direct or further class switching to IgE are the principle factors responsible for long-lasting sensitization of mast cells in allergic children. Indirect class switching from IgG producing plasma cells has been shown to be the predominant pathway for production of IgE while a Th2 microenvironment, genetic predisposition, and the concentration and nature of allergens together act on IgG plasma cells in the atopic tendency to undergo further immunoglobulin gene recombination. The seminal involvement of IgG in allergy is further indicated by the principal role of IgG4 in the natural resolution of allergy and as the favourable immunological response to immunotherapy. This paper will look at allergy through the role of different antibodies than IgE and give current knowledge of the nature and role of IgG antibodies in the start, maintenance and resolution of allergy.

Keywords: Allergy; antibodies; cells; mast cells/basophils; molecules; processes.

Figures

Figure 1
Figure 1
B Cell Maturation and Antibody Class Switching. A: The heavy gene on chromosome 22 consists of many alternative V, D, and J sequences which are deleted except for one sequence each as a loop of excised chromosomal DNA in a process of recombination during B cell maturation in the bone marrow. In the mature B cell the antibody class genes are spliced by switch regions against the chosen VDJ sequence to generate and full antibody protein carried on the surface. In allergy IgE switched B cells can be generated indirectly via IgG producing B cells or switch directly to IgE production. B: Antibody switching in mature B cells is influenced by cytokines produced by T helper cells. IFNγ generates IgG1 and IgG3 secreting plasma cells in the blood while IL4 may generate either IgG4 or IgE producing cells.
Figure 2
Figure 2
Modular Structure of an IgG antibody. Antibodies are composed of globular domains, 4 per heavy chain, heavy‐chain variable (VH), first, second and third constant (CH1, CH2, and CH3) domains, 2 per light chain, variable (VL) and constant (CL) domains, held together in a strong barrel shape by intrachain disulphide bonds. Light and heavy chains are linked by interchain disulphide bonds. Different domains have different functions, the top domain of both the light and heavy chains carry unique complementarity determining regions (CDR) which project and interact with antigen as loops of unique sequence. Interaction with complement or cellular receptors is the function of CH2 and CH3 domains comprising the Fc portion of antibody. The serine residue at position 228 in the hinge region and the arginine at position 409 within the CH3 domain of IgG4 are indicated.
Figure 3
Figure 3
Immunomodulation by IgG4. A: blocking of IgE antibodies. IgG4 antibodies dissociate, mop up free allergen and fail to trigger Fc receptors. B: IL10 production by T regulatory cell, monocytes, macrophages, and DCs induces B cell production of IgG4. C: signaling through inhibitory FCγIIB receptors. ITIM inhibitory stimulus of FCγIIB ligated receptors without crosslinking by half or whole IgG4 prevents mast cell activation through FcγIII. formula image = IgE, formula image = IgG1, formula image = IgG4 vs Fel d1, formula image = IgG4 vs Der p1.

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