Role of IgG4 in ï list a mine Release from Human Basophil Leucocytes

Abstract

Several conflicting reports on the ability of IgG4 to mediate type I allergic reactions have appeared lately. We have developed a model system for testing this possibility, using passive sensitization of basophil leuocytes from normal individuals. At first, the system was optimized with regard to donor cells and anti-IgG4 antibody: among 3 normal individuals with cells showing high, medium and low responses to anti-IgE, only the high responder showed a reproducible, but low response to anti-IgG4. This response was consistent when testing anti-IgG4 from different sources, and could be potentiated by a phorbol ester TPA, although not up to the level of anti-IgE. The cells from the high responding donor and a monoclonal anti-IgG4 were selected for further studies. Serum pools from patients allergic to house dust mite (Dermatophagoides pteronyssinus) were used for passive sensitization. The pools contained allergen-specific IgE with or without concomitant IgG4 of the same specificity. The sensitized basophils reacted to anti-IgE and allergen, but to anti-IgG4 only to a small extent. However, when these serum pools were fractionated by affinity chromatography, only the IgE fractions and not the IgG4 fractions made the cells reactive towards specific allergen. It was still possible to elicit a reaction by triggering IgE with anti-IgE. whereas only a small reaction was seen, when IgG4-sensitized basophils were provoked with antí-IgG4. We conclude that IgG4 does not sensitize normal basophils.

Histamine release from gut mast cells from patients with inflammatory bowel diseases.

“…The corresponding basophils were not responsive to anti-IgG4, confirming previous findings. 12 FMLP is a potent histamine secretagogue in human basophils and these results show that in mast cell dispersates no significant histamine release was induced. This indicates that dispersates were not contaminated with basophils.…”

Pulmonary immune cells in health and disease: mast cells and basophils

“…The f-met peptide and the complement peptides will both initiate histamine release in basophils from a wide range of donors, though the complement peptides are "incomplete" stimuli and fail to initiate leukotriene release unless the basophils have been primed [81,82]. In contrast, IgG triggers degranulation in only a small percentage of donors [83], and it is not clear if the levels of IgG required could be attained in vivo. Basophils also possess a receptor for prostaglandin D 2 (PGD 2 ) [77,78], which is linked to the generation of cAMP and may act in an autocrine negative feedback fashion.…”

“…SCF initiates degranulation in skin mast cells [132], and primes lung mast cells to a subsequent IgE-mediated challenge [83], but fails to trigger histamine release in dispersed lung mast cells [83,132].…”

“…Elucidating the mechanisms responsible for this mast cell priming would clearly be of interest, and yet most studies of cytokine priming have focused on the ability of cytokines to increase IgE-dependent histamine release, rather than an increase in sensitivity to IgE crosslinking. Extensive surveys of the interactions between cytokines and human mast cells have, with the exception of SCF [83], failed to identify any cytokines which modulate mast cell releasability. SCF enhanced IgEdependent activation of human lung mast cells, without initiating mediator release alone [83].…”

“…Extensive surveys of the interactions between cytokines and human mast cells have, with the exception of SCF [83], failed to identify any cytokines which modulate mast cell releasability. SCF enhanced IgEdependent activation of human lung mast cells, without initiating mediator release alone [83]. The concentrations of SCF required to obtain maximal priming are between 1-10 ng·ml -1 , values close to those identified in plasma [132], suggesting that physiological concentrations of SCF could well be relevant to mast cell releasability.…”