Mast cell FcεRI density and function dissociate from dependence on soluble IgE concentration at very low and very high IgE concentrations

摘要

Objective. The contribution of affinity, clonality, and concentration of individual IgE species to effector cell response has recently been characterized in a model with recombinant human IgE on passively sensitized basophils. This study extends the dependence of effector cell degranulation on IgE concentration to mast cells cultured with IgE for 2 weeks. Methods. Human mast cells cultured for 7 weeks from peripheral blood stem cells were matured for 2 weeks with interleukin-4 (IL-4) and recombinant human IgE consisting of two clones specific for Dermatophagoides pteronyssinus 2 (Derp2) (7% + 7%) and unspecific IgE at 0.8, 8, 80, and 800 kU/L. The density of the IgE receptor, FcεRI, and mast cell function were measured after challenging with recombinant Derp2 at 14 concentrations from 10 fg/mL to 100 pg/mL. CD63 expression, histamine release, and Prostaglandin D2 (PGD2) synthesis were measured, and maximal expression and mast cell sensitivity were calculated. Results. At 800 kU/L IgE, FcεRI expression varied more than at 80, 8, and 0.8 kU/L IgE. There was a trend toward increased maximal expression of CD63, histamine release, and PGD2 secretion with increasing IgE concentration. At 0.1 kU/L specific IgE, the LC50 increased up to fivefold, least so for PGD2. Conclusions. Human mast cells cultured with rhIgE of known composition are a sensitive model for studying factors governing effector cell degranulation that is close to the in vivo situation. This model can be used to study effects of IgE concentration, clonality, and affinity and may help predict the optimal immunologic treatment for a given patient.