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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

Analyses of B cells from paired samples of blood (B) and synovial				tissue from both the right (R) and left (L) hips of the same rheumatoid				arthritis patient. Results using both the genomic DNA-based assay and the				complementary (c)DNA-based assay for the three major immunoglobulin isotypes				(M, G, and A) are shown. R, clones that are restricted to the right hip joint;				L, clones that are restricted to the left hip joint; R+L, clones that are				common to both the right and left hip joints.
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Figure 4: Analyses of B cells from paired samples of blood (B) and synovial tissue from both the right (R) and left (L) hips of the same rheumatoid arthritis patient. Results using both the genomic DNA-based assay and the complementary (c)DNA-based assay for the three major immunoglobulin isotypes (M, G, and A) are shown. R, clones that are restricted to the right hip joint; L, clones that are restricted to the left hip joint; R+L, clones that are common to both the right and left hip joints.

Mentions: In order to confirm that these clonally expanded B cells were receiving ongoing antigenic stimulation and not limited solely to the memory compartment, we employed the cDNA-based assay to distinguish clonal expansions of activated B cells from resting (memory) cells. As illustrated in Figure 2, activated B-cell clones (identified by the letter 'A' in Fig. 2) expressing each of the immunoglobulin heavy-chain isotypes were easily identified in all the VH families studied. In some instances, these activated clones were also expanded numerically (as defined by the genomic DNA-based assays, and identified by the letter 'E' in Fig. 2). In other cases, these activated clones did not appear to be numerically expanded. Similar examples can be found in Figures 3 and 4, but they are not identified by letters in order to simplify the Figures.


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)

Analyses of B cells from paired samples of blood (B) and synovial				tissue from both the right (R) and left (L) hips of the same rheumatoid				arthritis patient. Results using both the genomic DNA-based assay and the				complementary (c)DNA-based assay for the three major immunoglobulin isotypes				(M, G, and A) are shown. R, clones that are restricted to the right hip joint;				L, clones that are restricted to the left hip joint; R+L, clones that are				common to both the right and left hip joints.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Analyses of B cells from paired samples of blood (B) and synovial tissue from both the right (R) and left (L) hips of the same rheumatoid arthritis patient. Results using both the genomic DNA-based assay and the complementary (c)DNA-based assay for the three major immunoglobulin isotypes (M, G, and A) are shown. R, clones that are restricted to the right hip joint; L, clones that are restricted to the left hip joint; R+L, clones that are common to both the right and left hip joints.
Mentions: In order to confirm that these clonally expanded B cells were receiving ongoing antigenic stimulation and not limited solely to the memory compartment, we employed the cDNA-based assay to distinguish clonal expansions of activated B cells from resting (memory) cells. As illustrated in Figure 2, activated B-cell clones (identified by the letter 'A' in Fig. 2) expressing each of the immunoglobulin heavy-chain isotypes were easily identified in all the VH families studied. In some instances, these activated clones were also expanded numerically (as defined by the genomic DNA-based assays, and identified by the letter 'E' in Fig. 2). In other cases, these activated clones did not appear to be numerically expanded. Similar examples can be found in Figures 3 and 4, but they are not identified by letters in order to simplify the Figures.

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