Inhibition of Reagin-Mediated PCA Reactions in Monkeys and Histamine Release from Human Leukocytes by Human IgG₄ Subclass

Abstract

Human myeloma proteins of IgG₄ subclass in contrast to myeloma proteins IgG₁, IgG₂ and IgG₃, were capable of blocking PCA reactions in monkeys mediated by human reaginic antibodies of IgE class. In addition to IgE, IgG₄ myeloma protein was also capable of sensitizing leukocytes from normal individuals and gave histamine release (HR) upon challenge with anti-human IgG₄. Leukocytes from 11 allergic individuals and from 9 normal subjects sensitized with the serum of allergic patients, were capable of releasing histamine with anti-human IgG₄, anti-human IgE, and the specific allergen. No response was obtained with anti-human IgG₁ and IgG₃ sera. Leukocytes from the normal individuals released histamine from 3 to 20% with anti-human IgG₄ and from 6 to 30% with anti-human IgE. Moreover, normal leukocytes sensitized with IgG₄ myeloma protein or a serum of an allergic patient heated at 56°C for 2 h, released a significant amount of histamine on challenge with anti-human IgG₄ whereas no response was obtained with anti-human IgE. The biological role of human IgG₄ in immediate hypersensitivity reactions is discussed in relation to human IgE.

IgE and IgG4 Antibodies in Specific Human Allergies

“…Further more, a high incidence of IgG4 antibodies to castor bean allergen has been described in allergic patients [9]. These results are corroborated by those of Vijay et al [18] with ragweed pollen, who also demonstrated histamine release from human leukocytes mediated by human IgG4 subclass.…”

“…It has been inferred that IgG4 acts as a blocking antibody [11,17,18], No inverse relationship between serum-blocking anti body titer and reagin titer could be estab lished by Ishizaka et al [14] and Dieges [10] in patients with hay fever receiving im munotherapy.…”

Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors.

“…Human basophils express FcyRII (8), but no FcyRIII, and they failed to release histamine when challenged with anti-FcyRII (C. Lawrence and M. Daeron, unpublished data). Ancient experiments aiming at demonstrating the ability of IgG immune complexes to trigger histamine release in human basophils were contradictory (14,15). Human FcyRII are of two types: FcyRIIA/C and FcyRIIB.…”

Improvement of specific immunotherapy by human IgG and modified allergens

“…IgG4 has been suggested to have homocytotropic properties (120,121) but these results have not been confirmed by us (95) or others (115,116).…”