Allergen-specific IgE production of committed B cells from allergic patients in vitro.
The allergen-specific in vitro IgE synthesis in blood leukocytes from patients with allergy was monitored outside the pollen season with recombinant and natural pollen allergens and was compared with the total IgE production. The addition of interleukin-4 (IL-4) and antibody to CD40 increased the amount of total IgE by up to 20-fold in the culture supernatants of peripheral blood leukocytes from patients with allergy that could be antagonized by a neutralizing anti-IL-4 antibody in a dose-dependent manner. In contrast to total IgE, the amount of allergen-specific IgE was not affected by IL-4, and anti-CD40 or anti-IL-4, treatment. With oligonucleotides specific for IgE, complementary DNA from the amino terminal of the IgE heavy chain could be reversely transcribed and amplified by polymerase chain reaction from RNA of patients' unstimulated blood leukocytes, indicating that the IgE secretion in the cultures is due to a de novo IgE synthesis. It is concluded that the peripheral blood of patients with allergy contains long-lived allergen-specific B cells, which are not responsive to IL-4-mediated signals. These results may have implications for attempts to modulate specific IgE production in allergic patients with cytokines or cytokine antagonists.
Steinberger
P
P
Institute of General and Experimental Pathology, General Hospital, University of Vienna, Austria.
Bohle
B
B
di Padova
F
F
Wrann
M
M
Liehl
E
E
Scheiner
O
O
Kraft
D
D
Valenta
R
R
D000485:Allergens / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D019013:CD40 Antigens; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000276:immunology
D000485:Allergens; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E