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

  • S Ruzickova1,

    Affiliated with

    • O Krystufkova1,

      Affiliated with

      • L Sedova1,

        Affiliated with

        • J Niederlova1,

          Affiliated with

          • Z Cimburek2,

            Affiliated with

            • T Dörner3 and

              Affiliated with

              • J Vencovsky1

                Affiliated with

                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, Charité

                Copyright

                © BioMed Central Ltd 2004

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