Estimation of polyclonal Ig<scp>G</scp>4 hybrids in normal human serum

Young, Elizabeth A.; Lock, Emma; Ward, Douglas G.; Cook, Alex; Harding, Stephen; Wallis, Gregg

doi:10.1111/imm.12265

Cited by 25 publications

(22 citation statements)

References 28 publications

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“…25 Furthermore, hybrid IgG4 antibodies containing both a kappa and a lambda light chain have been demonstrated in sera from healthy individuals. 36 The functional consequences of Fab arm exchange are at least twofold. First, the exchange appears to be essentially a random process, and one specificity will combine with any number of other, usually unrelated specificities in the other Fab arm.…”

Section: Fab Arm Exchangementioning

confidence: 99%

The Immunobiology of Immunoglobulin G4

Lighaam

Rispens

2016

Semin Liver Dis

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Human immunoglobulin G4 (IgG4) antibodies are in many ways unusual. In this review, an overview is given of the structural and functional aspects of IgG4 antibodies, the consequences of IgG4 antibody formation in various disease settings, and the factors involved in the regulation of IgG4 responses. Unlike most IgG antibodies, IgG4 antibodies exist in a dynamic equilibrium with other IgG4 antibodies, continuously exchanging half-molecules resulting in effectively monovalent antibodies that cannot cross-link. Together with the low affinities to C1q and most Fc receptors, and a generally high affinity for antigen, IgG4 antibodies appear to be nature's way of producing "blocking antibodies." On the one hand, IgG4 may contribute to tolerance to allergens, presumably via competition with IgE. Also, IgG4 immune responses to filarial parasites might prevent excessive immune reactions during such infections. On the other hand, IgG4 autoantibodies may be pathogenic, simply because they inhibit the function of their target molecules. Furthermore, IgG4 antibodies to biologicals may result in secondary loss of response. In addition, IgG4 has been implicated to impair humoral immunity to tumors. The role of high IgG4 serum levels in IgG4-related disease has not yet been established. Regulation of IgG4 responses is most likely a multifactorial process, which in vivo requires prolonged or repeated challenge with antigen, and is associated with regulatory T cells, T helper 2 cells, interleukin- (IL-) 4, and IL-10. In vitro, cytokines like IL-4, IL-13, IL-10, and IL-21 have been shown to differentially influence IgG4 production. The properties of IgG4 B cells have now started to be elucidated, and may provide additional clues to explain the unusual dynamics of IgG4-antibody responses.

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Section: Fab Arm Exchangementioning

confidence: 99%

The Immunobiology of Immunoglobulin G4

Lighaam

Rispens

2016

Semin Liver Dis

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“…Van der Neut Kolfschoten et al estimated that 50% of two IgG4 murine monoclonal antibodies against Fel d1 antigen and Bet v1 antigen underwent Fab arm exchange between when administered to immunodeficent SCID mice. The presence of both κ and λ light chains on 21–33% of IgG4 molecules of five sera tested indicate that Fab exchange occurs in a substantial portion of IgG4 in human serum . Bivalent IgG4 molecules have much less affinity to either antigen, reducing inflammation more effectively than clearing antigen .…”

Section: Introductionmentioning

confidence: 99%

Immunoglobulin G; structure and functional implications of different subclass modifications in initiation and resolution of allergy

Scott-Taylor

Axinia

Amin

et al. 2017

Immunity Inflam & Disease

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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.

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“…IgG4 antibodies that have undergone this process are consequently unable to undergo antigen cross-linking to form immune complexes. Analysis of serum from healthy human subjects revealed that 20–30 % of monomeric IgG4 contained both κ and λ light chains within the same molecule, demonstrating that Fab arm exchange occurs in vivo in a substantial fraction of IgG4 [ 14 •].…”

Section: Introductionmentioning

confidence: 99%

Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity Reactions

James

Till

2016

Curr Allergy Asthma Rep

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IgG4 is the least abundant IgG subclass in human serum, representing less than 5 % of all IgG. Increases in IgG4 occur following chronic exposure to antigen and are generally associated with states of immune tolerance. In line with this, IgG4 is regarded as an anti-inflammatory antibody with a limited ability to elicit effective immune responses. Furthermore, IgG4 attenuates allergic responses by inhibiting the activity of IgE. The mechanism by which IgG4 inhibits IgE-mediated hypersensitivity has been investigated using a variety of model systems leading to two proposed mechanisms. First by sequestering antigen, IgG4 can function as a blocking antibody, preventing cross-linking of receptor bound IgE. Second IgG4 has been proposed to co-stimulate the inhibitory IgG receptor FcγRIIb, which can negatively regulate FcεRI signaling and in turn inhibit effector cell activation. Recent advances in our understanding of the structural features of human IgG4 have shed light on the unique functional and immunologic properties of IgG4. The aim of this review is to evaluate our current understanding of IgG4 biology and reassess the mechanisms by which IgG4 functions to inhibit IgE-mediated allergic responses.

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Estimation of polyclonal IgG4 hybrids in normal human serum

Cited by 25 publications

References 28 publications

The Immunobiology of Immunoglobulin G4

The Immunobiology of Immunoglobulin G4

Immunoglobulin G; structure and functional implications of different subclass modifications in initiation and resolution of allergy

Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity Reactions

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