title: Frequency analysis of IgE-secreting B lymphocytes in persons with normal or elevated serum IgE levels.
abstract: The immunoregulatory mechanisms that determine the high serum IgE antibody levels in disorders such as helminth parasite infections and the hyper-IgE recurrent infection syndrome (HIE) remain poorly understood. To assess whether elevated serum IgE levels result from an increased number of B lymphocytes committed to IgE production, the proportion of IgE-producing B lymphocytes was determined by a filter immunoplaque assay using PBMC from persons with a broad range of serum IgE levels that included normal persons (n = 9) and patients with loiasis (n = 12), tropical pulmonary eosinophilia (TPE) (n = 6), lymphatic filariasis (n = 28), and HIE (n = 8). PBMC from these persons were assessed for production of in vitro IgE. The geometric mean number of IgE-secreting cells in 10(5) B lymphocytes in PBMC was 0.42 (range 0-2.2) in normal persons, 5.6 (range 0.1-35.5) among patients with loiasis, 9.4 (range 0-53.2) among patients with lymphatic filariasis, 52 (range 31.5-115) among patients with TPE, and 218 (range 56-1404) among patients with HIE. When all study subjects were grouped, there were significant correlations with serum IgE levels (r2 = 0.78; p less than 0.0001) and net spontaneous in vitro IgE production (r2 = 0.8; p less than 0.0001). Estimates of the amount of IgE production per B lymphocyte were similar among normal persons, patients with filarial infections, and patients with TPE (geometric means of 134, 96, and 141 pg/ml/cell, respectively); in contrast, for HIE patients, IgE production by individual B cells was significantly lower (geometric mean 28 pg/ml/cell; p less than 0.001). These observations demonstrate that clonal expansion of IgE-producing B lymphocytes is a major mechanism underlying the elevated serum IgE levels seen in persons with hyper-IgE states.
authors.affiliation: Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD 20814.
authors.forename: C L
authors.initials: CL
authors.lastname: King
authors.forename: R W
authors.initials: RW
authors.lastname: Poindexter
authors.forename: J
authors.initials: J
authors.lastname: Ragunathan
authors.forename: T A
authors.initials: TA
authors.lastname: Fleisher
authors.forename: E A
authors.initials: EA
authors.lastname: Ottesen
authors.forename: T B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism*; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006462:Hemolytic Plaque Technique; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged
chemical_list: D007073:Immunoglobulin E; D007371:Interferon-gamma