The influence of recombinant mediators on in vitro IgG subclass secretion by peripheral blood mononuclear cells from patients with hypogammaglobulinemia and from normal donors.
Patients with hypogammaglobulinemia have recurrent infections and fail to produce protective antibodies. In order for B cells to mature into antibody producing cells, several other cell types such as macrophages and helper T lymphocytes must be involved. They secrete several mediators such as interleukin-1 (IL-1), IL-4, IL-5, IL-6 and interferon-gamma (IFN-gamma). These factors, as recombinant mediators, were tested to assess their ability to correct the immunoglobulin production defect in vitro from pokeweed mitogen (PWM) stimulated cultures of peripheral blood mononuclear cells (PBMC) from 11 patients with hypogammaglobulinemia, and from 10 normals as controls. In general, PBMC from hypogammaglobulinemic patients secreted very little Ig in cultures, and no mediator induced a statistically significant increase in the secretion of any IgG subclass. When assessed on an individual basis, one patient demonstrated a variable pattern of increase in total IgG, IgG1, and IgG3, secretion induced by various mediators, to within one standard deviation of the average secretion of normal PBMC cultured in PWM. In the case of the normal cells, IL-4, IL-6 and IL-1 plus IL-4 were able to increase IgG2 secretion in culture with PWM. No increase in secretion of IgG1, IgG3 and IgG4 or total IgG was demonstrable however. Hence, although there is variability in responsiveness amongst the patients, there does not appear to be any one of these recombinant mediators which will correct the defect.(ABSTRACT TRUNCATED AT 250 WORDS)
Matheson
D S
DS
Department of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Hart
L J
LJ
Webb
B T
BT
Yeoh
E
E
Ling
Z D
ZD
Junker
A K
AK
Tingle
A J
AJ
D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology*
D007074:Immunoglobulin G; D007378:Interleukins; D011994:Recombinant Proteins; D007371:Interferon-gamma