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Clonal expansion is a characteristic feature of the B-cell repetoire of patients with rheumatoid arthritis.

Itoh K, Patki V, Furie RA, Chartash EK, Jain RI, Lane L, Asnis SE, Chiorazzi N - Arthritis Res. (2000)

Bottom Line: These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells.Furthermore, some of these individual expansions can persist over extended periods of time.A determination of the targets of these autoimmune reactions may provide valuable clues to help understand the immunopathogenesis of this disease

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, New York 11030, USA.

ABSTRACT
The present study was designed to analyze the level of B-cell clonal diversity in patients with rheumatoid arthritis by using HCDR3 (third complementarity determining region of the rearranged heavy chain variable region gene) length as a marker. A modified immunoglobulin VH gene fingerprinting method using either genomic DNA or complementary (c)DNA derived from B cells of the peripheral blood, synovial fluid, and tissues of several rheumatoid arthritis patients was employed. These assays permitted the detection and distinction of numerically expanded B-cell clones from activated but not numerically expanded B-cell clones. The present data suggest that B-cell clonal expansion is a common and characteristic feature of rheumatoid arthritis and that it occurs with increasing frequency from the blood to the synovial compartments, resulting in a narrowing of the clonal repertoire at the synovial level. These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells. Furthermore, some of these individual expansions can persist over extended periods of time. These findings support the hypothesis that a chronic ongoing (auto)immune reaction is operative in rheumatoid arthritis and that this reaction, at least at the B-cell level, may be unique to each individual joint. A determination of the targets of these autoimmune reactions may provide valuable clues to help understand the immunopathogenesis of this disease

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Related in: MedlinePlus

Schematic representation of the two-stage VH				fingerprinting assay using either genomic DNA or complementary (c)DNA as				templates. In stage I for the genomic DNA-based assay, genomic DNA was				amplified using a sense VH family-specific FR1 primer in conjunction				with an antisense JH consensus primer. For the cDNA-based assay,				cDNA was amplified using a sense VH family-specific FR1 primer in				conjunction with the appropriate antisense CH primer. In stage II, polymerase				chain reaction (PCR) products generated from either genomic DNA or cDNA were				amplified using a nested sense VH family-specific FR3 primer and a				radiolabeled antisense nested JH consensus primer that had been				end-labeled with γ32-P. The radiolabeled PCR products were				electrophoresed through a 6% denaturing acrylamide sequencing gel, and then				exposed to photographic film overnight. See text (Materials and methods) for				further details. *Areas of coding end processing at the				D-JH and VH-DJH junctions. The VH				fingerprinting results displayed were derived with the cDNA-based assay.
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Figure 1: Schematic representation of the two-stage VH fingerprinting assay using either genomic DNA or complementary (c)DNA as templates. In stage I for the genomic DNA-based assay, genomic DNA was amplified using a sense VH family-specific FR1 primer in conjunction with an antisense JH consensus primer. For the cDNA-based assay, cDNA was amplified using a sense VH family-specific FR1 primer in conjunction with the appropriate antisense CH primer. In stage II, polymerase chain reaction (PCR) products generated from either genomic DNA or cDNA were amplified using a nested sense VH family-specific FR3 primer and a radiolabeled antisense nested JH consensus primer that had been end-labeled with γ32-P. The radiolabeled PCR products were electrophoresed through a 6% denaturing acrylamide sequencing gel, and then exposed to photographic film overnight. See text (Materials and methods) for further details. *Areas of coding end processing at the D-JH and VH-DJH junctions. The VH fingerprinting results displayed were derived with the cDNA-based assay.

Mentions: The original immunoglobulin VH gene fingerprinting assay [23] was modified into two stages, starting with either genomic DNA or cDNA as templates (Fig. 1). The sequences of the primers used in these reactions were published previously [28].


Clonal expansion is a characteristic feature of the B-cell repetoire of patients with rheumatoid arthritis.

Itoh K, Patki V, Furie RA, Chartash EK, Jain RI, Lane L, Asnis SE, Chiorazzi N - Arthritis Res. (2000)

Schematic representation of the two-stage VH				fingerprinting assay using either genomic DNA or complementary (c)DNA as				templates. In stage I for the genomic DNA-based assay, genomic DNA was				amplified using a sense VH family-specific FR1 primer in conjunction				with an antisense JH consensus primer. For the cDNA-based assay,				cDNA was amplified using a sense VH family-specific FR1 primer in				conjunction with the appropriate antisense CH primer. In stage II, polymerase				chain reaction (PCR) products generated from either genomic DNA or cDNA were				amplified using a nested sense VH family-specific FR3 primer and a				radiolabeled antisense nested JH consensus primer that had been				end-labeled with γ32-P. The radiolabeled PCR products were				electrophoresed through a 6% denaturing acrylamide sequencing gel, and then				exposed to photographic film overnight. See text (Materials and methods) for				further details. *Areas of coding end processing at the				D-JH and VH-DJH junctions. The VH				fingerprinting results displayed were derived with the cDNA-based assay.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC17803&req=5

Figure 1: Schematic representation of the two-stage VH fingerprinting assay using either genomic DNA or complementary (c)DNA as templates. In stage I for the genomic DNA-based assay, genomic DNA was amplified using a sense VH family-specific FR1 primer in conjunction with an antisense JH consensus primer. For the cDNA-based assay, cDNA was amplified using a sense VH family-specific FR1 primer in conjunction with the appropriate antisense CH primer. In stage II, polymerase chain reaction (PCR) products generated from either genomic DNA or cDNA were amplified using a nested sense VH family-specific FR3 primer and a radiolabeled antisense nested JH consensus primer that had been end-labeled with γ32-P. The radiolabeled PCR products were electrophoresed through a 6% denaturing acrylamide sequencing gel, and then exposed to photographic film overnight. See text (Materials and methods) for further details. *Areas of coding end processing at the D-JH and VH-DJH junctions. The VH fingerprinting results displayed were derived with the cDNA-based assay.
Mentions: The original immunoglobulin VH gene fingerprinting assay [23] was modified into two stages, starting with either genomic DNA or cDNA as templates (Fig. 1). The sequences of the primers used in these reactions were published previously [28].

Bottom Line: These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells.Furthermore, some of these individual expansions can persist over extended periods of time.A determination of the targets of these autoimmune reactions may provide valuable clues to help understand the immunopathogenesis of this disease

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, New York 11030, USA.

ABSTRACT
The present study was designed to analyze the level of B-cell clonal diversity in patients with rheumatoid arthritis by using HCDR3 (third complementarity determining region of the rearranged heavy chain variable region gene) length as a marker. A modified immunoglobulin VH gene fingerprinting method using either genomic DNA or complementary (c)DNA derived from B cells of the peripheral blood, synovial fluid, and tissues of several rheumatoid arthritis patients was employed. These assays permitted the detection and distinction of numerically expanded B-cell clones from activated but not numerically expanded B-cell clones. The present data suggest that B-cell clonal expansion is a common and characteristic feature of rheumatoid arthritis and that it occurs with increasing frequency from the blood to the synovial compartments, resulting in a narrowing of the clonal repertoire at the synovial level. These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells. Furthermore, some of these individual expansions can persist over extended periods of time. These findings support the hypothesis that a chronic ongoing (auto)immune reaction is operative in rheumatoid arthritis and that this reaction, at least at the B-cell level, may be unique to each individual joint. A determination of the targets of these autoimmune reactions may provide valuable clues to help understand the immunopathogenesis of this disease

Show MeSH
Related in: MedlinePlus