title: Impaired up-regulation of CD86 in B cells of "type A" common variable immunodeficiency patients.
abstract: Common variable immunodeficiency (CVID) is characterized by defective B cell maturation and antibody formation resulting in low serum antibody levels of most or all Ig isotypes. A specific subgroup of patients ("type A") has normal numbers of mature surface (s)IgM / sIgD- positive circulating B cells. However, since these lymphocytes do not respond to in vitro stimulation by differentiation and Ig synthesis, they seem to suffer from so far unknown intrinsic defects. Analyzing the expression pattern of a large set of B cell activation-specific surface markers, we found that type A CVID patients show a highly reduced expression of the CD28 / CTLA-4 ligand CD86 (B7-2) and of the lymphocyte activation marker CDw137 when compared to B cells of healthy donors and non-type-A CVID patients. The lowered CD86 expression levels were found to correlate with reduced levels of CD86 mRNA. Since combined stimulation via B cell antigen receptor and CD40 cross-linking did not rescue the defects in CD86 and CDw137 expression, B cells of CVID type A patients resemble functionally unresponsive lymphocytes incapable of cooperating with T cells. The fact that these cells accumulate in type A CVID patients suggests a causal relationship with the pathogenesis of this disease.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Denz
authors.forename: H
authors.initials: H
authors.lastname: Eibel
authors.forename: H
authors.initials: H
authors.lastname: Illges
authors.forename: G
authors.initials: G
authors.lastname: Kienzle
authors.forename: M
authors.initials: M
authors.lastname: Schlesier
authors.forename: H H
authors.initials: HH
authors.lastname: Peter
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D017074:Common Variable Immunodeficiency / Q000145:classification* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell