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AB0174 Increased Proportion of CD38+Igd+ B Cells Contributes to Pathogenesis of Primary SjÖGren's Syndrome
  1. E. Ishioka,
  2. K. Yoshimoto,
  3. A. Nishikawa,
  4. K. Suzuki,
  5. T. Takeuchi
  1. Keio University School of Medicine, Tokyo, Japan

Abstract

Background Primary Sjögren's syndrome (pSS) is characterized by overproduction of autoantibodies against nuclei etc. and clinical manifestations caused by immune complexes, such as peripheral neuropathy, vasculitic lesions and hypocomplementemia. These denote B cell hyperactivity, which is considered to play a key role in pathogenesis of pSS. However, detailed molecular mechanisms of hyperactivation of B cells still remain to be clarified.

Objectives In the present study, we investigated the mechanism of the abnormal activation of B cells in pSS patients. To this end, we employed FACS to analyze surface markers of B cells such as CD38 and IgD, both of which characterize activated B cell subsets.

Methods Peripheral B cells were prepared from pSS patients (n=10) and age matched normal individuals (n=6) with anti-CD19-coated microbeads. CD19, CD38 and IgD-triple positive cells were prepared by a cell sorter from peripheral blood samples of normal individuals (n=3). Surface markers of B cells were analyzed with direct immunofluorescence by FACS. B cells were stimulated in vitro with a combination of an anti-IgM antibody, recombinant CD40 ligand (rhCD40L), recombinant human IL-4 (rhIL-4) and recombinant human soluble BAFF (rhsBAFF). The amounts of IgG in the culture supernatants were measured by ELISA.

Results FACS analysis of whole blood samples revealed that the proportion of CD38+IgD+ B cells among whole B cells, which represent an activated and differentiated B cell subset, was significantly higher in pSS patients than that in normal individuals (p=0.012). In addition, IgG production by pSS B cells was significantly increased as compared to normal B cells when the cells were stimulated in vitro with a combination of an anti-IgM antibody, rCD40L, rhIL-4 and rhsBAFF. Notably, the proportion of CD38+IgD+ was significantly and positively correlated with the serum IgG level among pSS patients (R2=0.5723). These results raise the possibility that increased serum IgG level in pSS patients was attributed to an increase in the population of this activated B cell subset. To address this issue, CD38+IgD+ B cells were prepared from normal individuals and IgG production in vitro was examined. Co-stimulation of this subset induced production of considerable amount of IgG, while the induction was only marginal with CD38+IgD, CD38IgD+ or CD38IgD subsets. These data collectively suggest that increase in a population of a CD38+IgD+ subset of B cells is responsible for increased serum IgG level in pSS patients.

Conclusions Our results suggest that abnormal increase in a population of CD38+IgD+ B cells is involved in IgG over production and hence in the pathogenesis of pSS.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.4060

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