The Genetics of Rheumatoid Factors (RF): The V-gene Repertoire of RFs in Rheumatoid Arthritis as Analyzed by Hybridoma Clones

Natvig, J. B.; Randen, Ingrid; Thompson, Keith M.; Førre, Ø.

doi:10.1007/978-3-642-76189-8_10

Cited by 8 publications

(15 citation statements)

References 47 publications

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“…These investigations extend and support earlier serologic studies of fine specificities and cross-reacting idiotypes of hybridomas and serum immunoglobulins of patients with RA and healthy controls [6][7][8][9]28,29].…”

Section: Discussionsupporting

confidence: 85%

“…A greater heterogeneity of RF from RA patients is further shown by their use of different isotypes and lambda light chains in addition to kappa chains [9]. This diversification of RF in RA patients leads to the hypothesis that these human RF are selected by an unknown antigen and have undergone somatic mutations in analogy to the MRL/lpr mouse model, where clonal expansion and accumulation of somatic mutations in antibody V regions could be demonstrated [10].…”

Section: Introductionmentioning

confidence: 99%

“…The cross-reacting idiotypes that characterize the light and heavy chains of paraproteins with RF activity have been demonstrated at significantly lower frequencies among RF produced by hybridomas established from synovial B cells of RA patients [6][7][8]. A greater heterogeneity of RF from RA patients is further shown by their use of different isotypes and lambda light chains in addition to kappa chains [9]. This diversification of RF in RA patients leads to the hypothesis that these human RF are selected by an unknown antigen and have undergone somatic mutations in analogy to the MRL/lpr mouse model, where clonal expansion and accumulation of somatic mutations in antibody V regions could be demonstrated [10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A somatically mutated VκIV gene encoding a human rheumatoid factor light chain

Gause

Küppers²,

Mierau

1992

Clinical and Experimental Immunology

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SUMMARY The light chain of an IgA K rheumatoid factor (RF) produced by a hybridoma derived from a patient with rheumatoid arthritis (RA) has been shown to belong to the VκIV family. This RF light chain has 31 nucleotide differences compared with the single VκIV germline gene reported for the human genome. The patient's VκIV germline gene was sequenced, using the polymerase chain reaction (PCR), and shown to be identical to that previously reported. This demonstrates that the RF light chain is the product of a somatically mutated gene. A comparison with other known VκIV sequences shows that the RF light chain has more replacement mutations than most of the known VKIV light chains.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A somatically mutated VκIV gene encoding a human rheumatoid factor light chain

Gause

Küppers²,

Mierau

1992

Clinical and Experimental Immunology

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“…The formation of ectopic lymphoid tissue is strongly associated with autoimmunity and autoantibody production in a variety of disorders (2), including the rheumatoid synovium (21,26), salivary glands in Sjogren’s syndrome (27), thymus in myasthenia gravis (19), and the thyroid in Hashimoto’s thyroiditis (28). In several examples of organ-specific autoimmune disease, autoreactive B cells have been found within ectopic lymphoid tissue in the target tissues.…”

Section: Discussionmentioning

confidence: 99%

Colocalization of Antigen-Specific B and T Cells within Ectopic Lymphoid Tissue following Immunization with Exogenous Antigen

Weinstein

Nacionales

Lee

et al. 2008

The Journal of Immunology

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Chronic inflammation promotes the formation of ectopic lymphoid tissue morphologically resembling secondary lymphoid tissues, though it is unclear whether this is a location where Ag-specific immune responses develop or merely a site of lymphocyte accumulation. Ectopic lymphoid tissue formation is associated with many humoral autoimmune diseases, including lupus induced by tetramethylpecadentane in mice. We examined whether an immune response to 4-hydroxy-3-nitrophenyl acetyl-keyhole limpet hemocyanin (NP-KLH) and NP-OVA develops within ectopic lymphoid tissue (“lipogranulomas”) induced by tetramethylpecadentane in C57BL/6 mice. Following primary immunization, NP-specific B cells bearing V186.2 and related heavy chains as well as λ-light chains accumulated within ectopic lymphoid tissue. The number of anti-NP-secreting B cells in the ectopic lymphoid tissue was greatly enhanced by immunization with NP-KLH. Remarkably, the H chain sequences isolated from individual lipogranulomas from these mice were diverse before immunization, whereas individual lipogranulomas from single immunized mice had unique oligo- or monoclonal populations of presumptive NP-specific B cells. H chain CDR sequences bore numerous replacement mutations, consistent with an Ag-driven and T cell-mediated response. In mice adoptively transferred with OT-II or DO11 T cells, there was a striking accumulation of OVA-specific T cells in lipogranulomas after s.c. immunization with NP-OVA. The selective colocalization of proliferating, Ag-specific T and B lymphocytes in lipogranulomas from tetramethylpecadentane-treated mice undergoing primary immunization implicates ectopic lymphoid tissue as a site where Ag-specific humoral immune responses can develop. This has implications for understanding the strong association of humoral autoimmunity with lymphoid neogenesis, which may be associated with deficient censoring of autoreactive cells.

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“…The murine anti-idiotypic (anti-Id) monoclonal antibodies (MoAb) G6 and G8 recognize structural determinants exclusive to V H 1-encoded antibodies [1,2]. The MoAbs G6 and/or G8 have been used in the idiotypic (Id) analyses of rheumatoid factors [1][2][3][4][5][6][7][8][9][10][11][12][13][14], and B lymphocytes from patients with chronic lymphocytic leukaemia (B-CLL) [15][16][17][18][19]. The goals of these studies were to determine whether there is a link between immunoglobulin (Ig) structures and specific diseases, and to probe for immunoglobulin gene usage.…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of the V_H1‐Specific Variable Region Determinants Recognized by Anti‐Idiotypic Monoclonal Antibodies G6 and G8

Potter

Mageed

et al. 1999

Scand J Immunol

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Mutational analysis was used to determine the structural basis for the binding of the murine anti-idiotypic (anti-Id) monoclonal antibodies (MoAb) G6 and G8 to VH1-encoded antibodies. The MoAb G6 binds a cross-reactive idiotope present on the heavy (H) chains of immunoglobulins (Ig) encoded by 51p1-related gene segments, but not those encoded by hv1263-related gene segments. Gene segments 51p1 (DP-10) and hv1263 differ by only four amino acids; three in complementarity-determining region 2 (CDR2), and one in framework region 3 (FR3). The MoAb G8 also binds 51p1-related sequences, although it is undetermined whether G8 can bind hv1263-related sequences. In order to localise the Ids recognized by MoAbs G6 and G8 on 51p1-encoded antibodies, recombinant antibodies containing H-chain mutants were expressed in insect cells. Idiotypic analysis on the expressed recombinant proteins definitively localised the reactivity in each molecule. These studies should be important in the structural appreciation for critical serological reagents.

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The Genetics of Rheumatoid Factors (RF): The V-gene Repertoire of RFs in Rheumatoid Arthritis as Analyzed by Hybridoma Clones

Cited by 8 publications

References 47 publications

A somatically mutated VκIV gene encoding a human rheumatoid factor light chain

A somatically mutated VκIV gene encoding a human rheumatoid factor light chain

Colocalization of Antigen-Specific B and T Cells within Ectopic Lymphoid Tissue following Immunization with Exogenous Antigen

Molecular Characterization of the V_H1‐Specific Variable Region Determinants Recognized by Anti‐Idiotypic Monoclonal Antibodies G6 and G8

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The Genetics of Rheumatoid Factors (RF): The V-gene Repertoire of RFs in Rheumatoid Arthritis as Analyzed by Hybridoma Clones

Cited by 8 publications

References 47 publications

A somatically mutated VκIV gene encoding a human rheumatoid factor light chain

A somatically mutated VκIV gene encoding a human rheumatoid factor light chain

Colocalization of Antigen-Specific B and T Cells within Ectopic Lymphoid Tissue following Immunization with Exogenous Antigen

Molecular Characterization of the VH1‐Specific Variable Region Determinants Recognized by Anti‐Idiotypic Monoclonal Antibodies G6 and G8

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Product

Resources

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Molecular Characterization of the V_H1‐Specific Variable Region Determinants Recognized by Anti‐Idiotypic Monoclonal Antibodies G6 and G8