title: Antibody-secreting cell specificity in labial salivary glands reflects the clinical presentation and serology in patients with Sjögren's syndrome.
abstract: OBJECTIVE
  The serologic hallmark of primary Sjögren's syndrome (SS) is the presence of IgG antibodies specific for Ro (SSA) and La (SSB). The molecular characteristics of gland-derived B cells at the site of primary SS inflammation have been described previously; however, parallels between glandular antibody-secreting cells (ASCs) and serologic antibody specificities have not been evaluated. We used recombinant monoclonal antibody (mAb) technology to study the specificities of salivary gland (SG)-derived ASCs, evaluate their molecular characteristics, and identify IgG antibody specificity.
  
  
  METHODS
  Human antibodies were generated from glandular IgG ASCs. Heavy chain and light chain use and immunoglobulin subclass were analyzed by sequencing. Enzyme-linked immunosorbent assay, indirect immunofluorescence, enzyme immunoassay, and (35) S-labeled protein immunoprecipitation analysis were used to determine antibody specificity.
  
  
  RESULTS
  Evaluation of single ASCs in SG biopsy specimens from a patient with primary SS and a patient with SS and overlapping systemic lupus erythematosus revealed significant concordance between serum autoantibody and glandular ASC specificities. Gland-derived ASC heavy chains and light chains were extensively somatically hypermutated, which is indicative of antigen-driven responses. Specifically, we produced the first fully human mAb derived from SGs.
  
  
  CONCLUSIONS
  In patients with SS, the SGs are a site for the production of antibodies that extend beyond the canonical Ro and/or La SS specificities. Glandular antibody production strongly reflected the serologic humoral response in the 2 patients whom we studied.
authors.affiliation: Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, and Oklahoma City VA Medical Center, Oklahoma City, and University of Texas at, El Paso.
authors.forename: Jacen S
authors.initials: JS
authors.lastname: Maier-Moore
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Koelsch
authors.forename: Kenneth
authors.initials: K
authors.lastname: Smith
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lessard
authors.forename: Lida
authors.initials: L
authors.lastname: Radfar
authors.forename: David
authors.initials: D
authors.lastname: Lewis
authors.forename: Biji T
authors.initials: BT
authors.lastname: Kurien
authors.forename: Nina
authors.initials: N
authors.lastname: Wolska
authors.forename: Umesh
authors.initials: U
authors.lastname: Deshmukh
authors.forename: Astrid
authors.initials: A
authors.lastname: Rasmussen
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Sivils
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.forename: A Darise
authors.initials: AD
authors.lastname: Farris
authors.forename: R Hal
authors.initials: RH
authors.lastname: Scofield
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology*; D000921:Antibody-Producing Cells / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D008046:Lip; D008875:Middle Aged; D012261:Ribonucleoproteins / Q000276:immunology; D012470:Salivary Glands, Minor / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D012261:Ribonucleoproteins; C035356:SS-A antibodies; C035357:SS-B antibodies