title: Production of autoantibodies against citrullinated antigens/peptides by human B cells.
abstract: Autoantibodies against citrullinated protein Ags (ACPA) are associated with the development of rheumatoid arthritis (RA). This immune response against citrullinated protein Ags, which is thought to be facilitated by certain MHC HLA-DR alleles, is highly specific for this disease and has been speculated to be involved in the pathogenesis. We have previously studied cultures of B cells for the production of Abs against HLA Ags. The aim of the current study was to examine the role of B cells in the production of ACPA in patients with RA. Peripheral blood B cells from RA patients and healthy people were cultured with EL4-B5, a murine cell line expressing human CD40L, and with T cell factors to stimulate the in vitro production of Abs by B cells isolated from peripheral blood. ACPA were produced by cultured B cells from RA patients, as determined by reactivity to cyclic citrullinated peptide (CCP). The results showed that 22% of the healthy persons tested also had B cells that could produce ACPA. Patients with HLA-DR alleles carrying the RA-associated shared epitope appeared to have more B cells with autoimmune potential for CCP than those without such HLA alleles (odds ratio 8.1, p = 0.001). In healthy individuals, anti-CCP-producing B cells were also observed more frequently if the RA-associated MHC genes were present (odds ratio 8.0, p = 0.01). Analysis of B cells in cultures may shed light on the interaction of genetic and environmental factors in the development of RA.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Bellatin
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.forename: Margarita
authors.initials: M
authors.lastname: Fallena
authors.forename: Lin
authors.initials: L
authors.lastname: Fan
authors.forename: Donglan
authors.initials: D
authors.lastname: Xia
authors.forename: Nancy
authors.initials: N
authors.lastname: Olsen
authors.forename: Valerie
authors.initials: V
authors.lastname: Branch
authors.forename: David
authors.initials: D
authors.lastname: Karp
authors.forename: Peter
authors.initials: P
authors.lastname: Stastny
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000918:Antibody Specificity; D015703:Antigens, CD / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured / Q000276:immunology; D002956:Citrulline / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D000939:Epitopes / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008223:Lymphoma / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D012907:Smoking / Q000097:blood / Q000276:immunology; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D000939:Epitopes; D006684:HLA-DR Antigens; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002956:Citrulline; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22