Volume 6 Supplement 1

24th European Workshop for Rheumatology Research

Open Access

Two B cell populations differentially expressing IgVH mRNAs in human RA synovium

  • S Ruzickova1,
  • O Krystufkova1,
  • L Sedova1,
  • J Niederlova1,
  • Z Cimburek2,
  • T Dörner3 and
  • J Vencovsky1
Arthritis Res Ther20046(Suppl 1):12

DOI: 10.1186/ar1054

Received: 16 January 2004

Published: 24 February 2004

Background

The lymphocytic infiltrates sometimes organized in ectopic germinal centres in rheumatoid arthritis (RA) synovium contain locally activated B cells expressing hypermutated immunoglobulin transcripts and recombination-activating genes (Rag), suggesting an ongoing antigen driven process directly in synovium.

Objective

To test this hypothesis, mutational frequencies of immunoglobulin mRNAs, signs of isotype switching and Rag gene expression in individual RA synovial B cells were analyzed.

Methods

Single-cell RT-PCR was used to analyze individual synovial CD19+CD38+ and CD19+IgM+ B cells (as the reference population) from two RA patients.

Results

We found significantly reduced frequencies of peripheral blood CD19+CD38+ B cells from RA patients as compared with controls, suggesting their possible migration into the site of inflammation. Three subsets of CD19+CD38+ B cells in RA synovium were detected, expressing (1) only IgM transcripts (IgM+, 13.5%), (2) only IgG transcripts (IgG+, 48.7%), and (3) both IgM and IgG mRNAs (IgM+IgG+, 37.8%). The differences in mutational frequencies between them were significant (Table 1). Over 40% of analyzed cells coexpressed Rag mRNAs. Similar subsets and expression patterns were found in CD19+IgM+ B cells; however, IgG+ cells displayed significantly decreased mutational frequencies (3.6%; P < 0.0001). This might reflect the presence of synovial B cell populations that differ in their maturational status or biological function.
Table 1

Mutational frequencies of IgVH mRNAs in RA synovial CD19+CD38+ and CD19+IgM+ populations

 

CD19+CD38+

CD19+IgM+

 

IgM+

IgM+IgG+

IgG+

IgM+

IgM+IgG+

IgG+

Total of nt

1761

6617

4683

2128

2570

2079

Mutated nt

94

465

462

75

110

75

MF (%)

5.3

7.0

9.9

3.5

4.3

3.6

Authors’ Affiliations

(1)
Institute of Rheumatology and LGE
(2)
Department of Immunology and Gnotobiology, CAS
(3)
Department of Rheumatology

Copyright

© The Author(s) 2004

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