Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity Reactions

TY - JOUR

T1 - Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity Reactions

AU - James, Louisa K.

AU - Till, Stephen J.

PY - 2016/3

Y1 - 2016/3

N2 - 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 Fc gamma RIIb, which can negatively regulate FceRI 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.

AB - 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 Fc gamma RIIb, which can negatively regulate FceRI 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.

KW - IgG4

KW - Hypersensitivity

KW - Blocking antibodies

KW - Allergy

KW - Allergen immunotherapy

KW - IgE

KW - FC-GAMMA-RIIB

KW - GRASS-POLLEN IMMUNOTHERAPY

KW - HUMAN MAST-CELLS

KW - MODIFIED TH2 RESPONSE

KW - FAB-ARM EXCHANGE

KW - HUMAN B-CELLS

KW - ALLERGEN IMMUNOTHERAPY

KW - IMMUNOGLOBULIN G4

KW - BLOCKING ANTIBODIES

KW - INHALANT ALLERGENS

U2 - 10.1007/s11882-016-0600-2

DO - 10.1007/s11882-016-0600-2

M3 - Literature review

SN - 1529-7322

VL - 16

JO - CURRENT ALLERGY AND ASTHMA REPORTS

JF - CURRENT ALLERGY AND ASTHMA REPORTS

IS - 3

M1 - 23

ER -