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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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Persistence of a synovial fluid B cell clone in the same joint for				4 months. Arthrocentesis was performed on the same joint of the same patient on				days 0 and 120. One of the B-cell clones identified in each of these samples				was identical in both HCDR3 length and in VHDJH gene DNA				sequence.
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Figure 5: Persistence of a synovial fluid B cell clone in the same joint for 4 months. Arthrocentesis was performed on the same joint of the same patient on days 0 and 120. One of the B-cell clones identified in each of these samples was identical in both HCDR3 length and in VHDJH gene DNA sequence.

Mentions: Figure 5 illustrates the best example of this phenomenon in a patient who was studied over a 4-month interval. The DNA-based assay using VH4 family-specific primers indicated the presence of two similar clones on days 0 and 120, whereas the other VH4-expressing clones detected at the first analysis were no longer present at the time of the second analysis. DNA sequence analyses of one of these two clones confirmed their identity, because each displayed the same rearranged VHDJH gene with identical VH mutations and identical HCDR3 sequences (data not shown). Therefore, certain clones can persist locally over time, suggesting that a common and persistent antigenic stimulation was operable in the joint of this rheumatoid arthritis patient.


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)

Persistence of a synovial fluid B cell clone in the same joint for				4 months. Arthrocentesis was performed on the same joint of the same patient on				days 0 and 120. One of the B-cell clones identified in each of these samples				was identical in both HCDR3 length and in VHDJH gene DNA				sequence.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Persistence of a synovial fluid B cell clone in the same joint for 4 months. Arthrocentesis was performed on the same joint of the same patient on days 0 and 120. One of the B-cell clones identified in each of these samples was identical in both HCDR3 length and in VHDJH gene DNA sequence.
Mentions: Figure 5 illustrates the best example of this phenomenon in a patient who was studied over a 4-month interval. The DNA-based assay using VH4 family-specific primers indicated the presence of two similar clones on days 0 and 120, whereas the other VH4-expressing clones detected at the first analysis were no longer present at the time of the second analysis. DNA sequence analyses of one of these two clones confirmed their identity, because each displayed the same rearranged VHDJH gene with identical VH mutations and identical HCDR3 sequences (data not shown). Therefore, certain clones can persist locally over time, suggesting that a common and persistent antigenic stimulation was operable in the joint of this rheumatoid arthritis patient.

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