Aberrant expression of BAFF by B lymphocytes infiltrating the salivary glands of patients with primary Sjögren's syndrome

Arthritis Rheum. 2007 Apr;56(4):1134-44. doi: 10.1002/art.22458.

Abstract

Objective: To identify the cells that produce BAFF in the salivary glands of patients with primary Sjögren's syndrome (SS), and to analyze BAFF receptor expression by local T and B lymphocytes.

Methods: We used 3 methods to identify the source of BAFF: in situ hybridization of the transcripts for BAFF combined with staining of membrane markers, regular and real-time reverse transcription-polymerase chain reaction (RT-PCR) of cultured epithelial cells, and RT-PCR of sorted single-cell T and B lymphocytes eluted from salivary glands. Cells expressing TACI, BCMA, and B lymphocyte stimulator receptor 3 (BR-3) were disclosed by combining each specific staining of the receptors with each specific staining of the cells. The function of BAFF generated by epithelial cells on B lymphocytes was determined in short-term cocultures.

Results: Transcripts for BAFF were seen in epithelial cells and infiltrating T lymphocytes and, for the first time, were detected in local B cells. It is interesting that BR-3 was present on these B cells but not on T cells. In contrast, TACI and, to a lesser degree, BCMA were observed on transitional B lymphocytes, whereas T lymphocytes were devoid of receptors for BAFF. Furthermore, this cytokine was shown to be functional, in that epithelial cell-bound BAFF extended the survival of normal B cells, but cell-free BAFF released in the supernatants did not.

Conclusion: These experiments establish that in primary SS, BAFF is produced not only by epithelial cells and T cells but also by B cells. The expression of receptors for BAFF would thus allow these receptors to participate in an autocrine pattern of self-stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Cell Activating Factor / biosynthesis*
  • B-Cell Activating Factor / genetics
  • B-Cell Maturation Antigen / genetics
  • B-Cell Maturation Antigen / metabolism
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Biomarkers / metabolism
  • Coculture Techniques
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression
  • Humans
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salivary Glands / anatomy & histology
  • Salivary Glands / metabolism*
  • Salivary Glands / pathology
  • Sjogren's Syndrome / metabolism*
  • Sjogren's Syndrome / pathology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Transmembrane Activator and CAML Interactor Protein / genetics
  • Transmembrane Activator and CAML Interactor Protein / metabolism
  • U937 Cells

Substances

  • B-Cell Activating Factor
  • B-Cell Maturation Antigen
  • BR-3 protein, human
  • Biomarkers
  • Neoplasm Proteins
  • RNA, Messenger
  • TNFRSF13B protein, human
  • TNFRSF17 protein, human
  • TNFSF13B protein, human
  • Transmembrane Activator and CAML Interactor Protein