title: Primary Sjögren's syndrome is characterized by distinct phenotypic and transcriptional profiles of IgD+ unswitched memory B cells.
abstract: OBJECTIVE
  The significance of distinct B cell abnormalities in primary Sjögren's syndrome (SS) remains to be established. We undertook this study to analyze the phenotype and messenger RNA (mRNA) transcript profiles of B cell subsets in patients with primary SS and to compare them with those in sicca syndrome patients and healthy controls.
  
  
  METHODS
  CD19+ B cells from 26 patients with primary SS, 27 sicca syndrome patients, and 22 healthy controls were analyzed by flow cytometry. Gene expression profiles of purified B cell subsets (from 3-5 subjects per group per test) were analyzed using Affymetrix gene arrays.
  
  
  RESULTS
  Patients with primary SS had lower frequencies of CD27+IgD- switched memory B cells and CD27+IgD+ unswitched memory B cells compared with healthy controls. Unswitched memory B cell frequencies were also lower in sicca syndrome patients and correlated inversely with serologic hyperactivity in both disease states. Further, unswitched memory B cells in primary SS had lower expression of CD1c and CD21. Gene expression analysis of CD27+ memory B cells separated patients with primary SS from healthy controls and identified a subgroup of sicca syndrome patients with a primary SS-like transcript profile. Moreover, unswitched memory B cell gene expression analysis identified 187 genes differentially expressed between patients with primary SS and healthy controls.
  
  
  CONCLUSIONS
  A decrease in unswitched memory B cells with serologic hyperactivity is characteristic of both established primary SS and a subgroup of sicca syndrome, which suggests the value of these B cells both as biomarkers of future disease progression and for understanding disease pathogenesis. Overall, the mRNA transcript analysis of unswitched memory B cells suggests that their activation in primary SS takes place through innate immune pathways in the context of attenuated antigen-mediated adaptive signaling. Thus, our findings provide important insight into the mechanisms and potential consequences of decreased unswitched memory B cells in primary SS.
authors.affiliation: University of Rochester Medical Center, Rochester, New York.
authors.forename: Mustimbo E P
authors.initials: ME
authors.lastname: Roberts
authors.forename: Denise
authors.initials: D
authors.lastname: Kaminski
authors.forename: Scott A
authors.initials: SA
authors.lastname: Jenks
authors.forename: Craig
authors.initials: C
authors.lastname: Maguire
authors.forename: Kathryn
authors.initials: K
authors.lastname: Ching
authors.forename: Peter D
authors.initials: PD
authors.lastname: Burbelo
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Iadarola
authors.forename: Alexander
authors.initials: A
authors.lastname: Rosenberg
authors.forename: Andreea
authors.initials: A
authors.lastname: Coca
authors.forename: Jennifer
authors.initials: J
authors.lastname: Anolik
authors.forename: Iñaki
authors.initials: I
authors.lastname: Sanz
mesh_terms: D000328:Adult; D000368:Aged; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012859:Sjogren's Syndrome / Q000276:immunology / Q000378:metabolism*
chemical_list: D007072:Immunoglobulin D