Abnormalities in peripheral B cell memory of patients with primary Sjögren's syndrome

Arthritis Rheum. 2004 Jun;50(6):1897-908. doi: 10.1002/art.20276.


Objective: To delineate disturbances in peripheral B cell memory in primary Sjögren's syndrome (SS).

Methods: Isotype-specific immunoglobulin (Ig) heavy-chain transcripts were analyzed in single-sorted CD19+,CD27- naive and CD19+,CD27+ memory B cells from patients with primary SS and normal healthy control subjects.

Results: A significantly higher frequency of B cells expressing mu-, alpha-, and/or gamma-chain transcripts were found in patients with primary SS compared with controls (58.0% versus 14.3%; P < 0.0001). Notably, 30.5% of individual B cells (for primary SS, 38.7%; for controls, 12.7% [P < 0.0001]) simultaneously expressed transcripts for different Ig heavy-chain isotypes using identical V(H)-D-J(H) rearrangements. However, these cells lacked surface expression of more than one of the respective Ig heavy-chain isotypes as well as messenger RNA (mRNA) transcripts for 2 germinal center markers, activation-induced cytidine deaminase, and Bcl-6. In contrast with the findings in normal healthy controls, peripheral B cell memory in patients with primary SS was characterized by 1) circulating CD27+ B cells expressing heavily mutated Ig V(H) transcripts (mutational frequency 8.6% versus 4.3%; P < 0.0001), 2) significantly enhanced mutational frequencies of C mu transcripts (9.6% versus 2.5%; P < 0.0001), 3) a high proportion (61.2%) of CD27+ B cells expressing transcripts for multiple Ig heavy-chain isotypes, and 4) a CD27- memory-type B cell subpopulation expressing mutated C mu transcripts.

Conclusion: Altogether, both B cell hyperactivity and striking abnormalities in peripheral B cell memory are indicated at the single-cell mRNA level in patients with primary SS. Detection of multiple Ig heavy-chain transcripts in peripheral CD19+,CD27+ memory B cells of patients with SS may represent the abnormal retention of pre-switch mRNA transcripts in circulating post-switch B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD19 / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Biomarkers
  • Complementarity Determining Regions / genetics
  • Complementarity Determining Regions / immunology
  • Cytidine Deaminase / genetics
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • Exonucleases / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Immunologic Memory / immunology*
  • Male
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger / analysis
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / physiopathology*
  • Transcription Factors / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism


  • Antigens, CD19
  • Biomarkers
  • Complementarity Determining Regions
  • DNA-Binding Proteins
  • Immunoglobulin Heavy Chains
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger
  • Transcription Factors
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Exonucleases
  • Cytidine Deaminase