Competitive Inhibition of Reagin-Mediated Histamine Release by a Human IgG2 Myeloma Protein

Abstract

Two human IgG myeloma proteins were isolated from other serum proteins based upon their fixation to monkey lung tissue. Electrophoretic and subclass studies revealed that the slow (γ₂) migrating protein belonged to the IgG1 subclass, and the fast (γ₁) migrating protein belonged to the IgG2 subclass. Competition experiments showed that the IgG2 myeloma protein competes for the same tissue-binding sites as human reagin. In addition, the IgG2 myeloma protein (1) loses its tissue-binding properties upon heating at 56 °C and treatment with mercaptoethanol, (2) gives reverse histamine release from monkey lung tissue challenged with rhesus antihuman IgG, and (3) fixes to monkey skin for at least 3 days. On the other hand, the IgG1 myeloma protein does not compete with human reagin for tissue-binding sites but apparently binds at separate, distinct receptor sites on monkey lung tissue.

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

“…These re sults suggest that IgG4 myelomas may in fact be heterogenous and possess different biological properties. Similar discrepancies have arisen with IgG2 myelomas and here again the idiotypic nature of these myeloma proteins may account for the different re sults reported [8,9,17], In a separate study [18], quantitation of serum IgE antibodies, using Phadebas RAST Kit, were compared with skin tests (i.d.) of 14 patients sensitive to a variety of allergens.…”

“…Since, the above blocking experiments were performed in heterologous (monkey) tissue, it would be interesting to determine if IgG4 can block the binding of IgE on human basophils. Ishi zaka et al [17] and Malley et al [9], em ploying different preparations of IgG., mye loma proteins in human and monkey, re spectively, failed to show the sensitization reaction (i.e. blocking activity).…”

“…Recently, inhibition of reaginmediated PCA reactions in baboons by hu man IgG4 and in monkeys by human IgG2 has been reported by Stanworth and Smith [8] and Malley et al [9], respectively.…”

IgG4 and Passive Sensitization of Basophil Leukocytes

“…Whereas most of the blocking activity of IgG on passive sensitization has been attri buted to IgG4 [5,7], Malley et al [6] found blocking activity in an IgG2-myeloma pro tein. Vijay and Perelmutter [7] suggested that IgG4-myeloma proteins may be hetero geneous and may have different biological activities.…”

“…Stanworth and Smith [5] have shown that myeloma protein of the IgG4 subclass inhibits reagin-mediated PCA reactions in baboons, whereas Malley et al [6] found that only IgG2-myeloma protein inhibited PCA reactions in monkeys. Vijay and Perelmutter [7] observed PCA inhibition in mon keys by IgG4-myeloma protein; they also described histamine release from human leukocytes, mediated by the IgG4 subclass.…”