title: IL-4 synergizes with IL-10 and anti-CD40 MoAbs to induce B-cell differentiation in patients with common variable immunodeficiency.
abstract: In the present study the phenotype and function of lymphocytes from patients with common variable immunodeficiency (CVI) were studied. Five out of 12 patients had abnormally low proportion of CD4+ T cells, but PBMC of these patients were capable of proliferating in response to polyclonal T-cell mitogens or PPD antigen. The phenotype of patients' B cells, as determined by expression of CD10, CD19 and CD34, was comparable to that of healthy controls. IL-4 and anti-CD40 MoAbs induced moderate B-cell differentiation in PBMC derived from patients with CVI, but the frequencies of Ig-secreting cells were generally at levels spontaneously observed in healthy controls. IL-10 was completely ineffective in inducing IgG-secreting cells in cultures of PBMC derived from patients with CVI even in the presence of anti-CD40 MoAbs, whereas high frequencies of Ig-secreting cells were induced under similar condition in cultures of PBMC derived from healthy controls. Importantly, when IL-4 was added to cultures stimulated with anti-CD40 MoAbs and IL-10, a very strong synergistic effect on the numbers of Ig-secreting cells and the levels of Ig secretion was observed in PBMC from both patients and controls. Moreover, the frequencies of Ig-secreting cells after activation with anti-CD40 MoAbs, IL-4 plus IL-10 in PBMC from some patients were comparable to those observed in PBMC from healthy controls. Taken together, these results indicate that B cells from patients with CVI have impaired capacity to differentiate into Ig-secreting cells in response to IL-10 and anti-CD40 MoAbs, and that this unresponsiveness can be restored by exogenous IL-4 in a proportion of the patients.
authors.affiliation: Department of Medical Microbiology, Turku University, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Punnonen
authors.forename: L
authors.initials: L
authors.lastname: Kainulainen
authors.forename: O
authors.initials: O
authors.lastname: Ruuskanen
authors.forename: J
authors.initials: J
authors.lastname: Nikoskelainen
authors.forename: H
authors.initials: H
authors.lastname: Arvilommi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018941:Antigens, CD19 / Q000032:analysis / Q000276:immunology; D018952:Antigens, CD34 / Q000032:analysis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000494:pharmacology; D017252:CD3 Complex / Q000032:analysis / Q000276:immunology; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D019013:CD40 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011043:Pokeweed Mitogens / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D014373:Tuberculin / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D018952:Antigens, CD34; D001426:Bacterial Proteins; D017252:CD3 Complex; D019013:CD40 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D018793:Interleukin-13; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014373:Tuberculin; C089436:anticoagulant protein, Streptomyces cinnamoneus; C047876:phytohemagglutinin-M; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; D017493:Leukocyte Common Antigens