Characterization of human-human hybridoma monoclonal anti-Ro(SS-A) autoantibodies derived from normal tonsil lymphoid cells

Massicotte, H; Harley, John B.; Bell, David A.

doi:10.1016/0896-8411(92)90192-s

Cited by 5 publications

(2 citation statements)

References 41 publications

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“…This becomes obvious when looking at the CDR3 regions of the anti-La mabs and is supported by the detailed sequence and epitope analysis. Although the hybridomas may go back to individual clones, the sequence supports the idea that both the truly autoreactive anti-La B cells and the anti-La B cells recognizing cryptic epitopes originate from a common pool of precursor B cells [55].…”

Section: Discussionmentioning

confidence: 61%

T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation

Bachmann

Bartsch

Bippes

et al. 2021

IJMS

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Since the first description of nuclear autoantigens in the late 1960s and early 1970s, researchers, including ourselves, have found it difficult to establish monoclonal antibodies (mabs) against nuclear antigens, including the La/SS-B (Sjögrens’ syndrome associated antigen B) autoantigen. To date, only a few anti-La mabs have been derived by conventional hybridoma technology; however, those anti-La mabs were not bona fide autoantibodies as they recognize either human La specific, cryptic, or post-translationally modified epitopes which are not accessible on native mouse La protein. Herein, we present a series of novel murine anti-La mabs including truly autoreactive ones. These mabs were elicited from a human La transgenic animal through adoptive transfer of T cells from non-transgenic mice immunized with human La antigen. Detailed epitope and paratope analyses experimentally confirm the hypothesis that somatic hypermutations that occur during T cell dependent maturation can lead to autoreactivity to the nuclear La/SS-B autoantigen.

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Section: Discussionmentioning

confidence: 61%

T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation

Bachmann

Bartsch

Bippes

et al. 2021

IJMS

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“…Thus some, although probably a minority, of the anti-DNA antibodies bind cardiolipin (23) and others have rheumatoid factor reactivity (24). More recently, it has been shown that human monoclonal antibodies may bind Ro and DNA (25). Thus, autoantibodies may be truly polyreactive.…”

mentioning

confidence: 99%

The Origin, Sequence, Structure, and Consequences of Developing Anti‐DNA Antibodies

Isenberg

Ehrenstein

Longhurst

et al. 1994

Arthritis & Rheumatism

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Although the etiology of systemic lupus erythematosus (SLE) remains enigmatic, it is likely that antibodies to DNA are an integral component in many, though not all, cases. The caveat is necessary, because several reports (for review, see ref. 1) have indicated that 30% or more of patients who meet the widely accepted classification criteria (2) devised by the American College of Rheumatology (formerly, the American Rheumatism Association) do not have detectable anti-DNA antibodies. Although useful, the classification criteria are broadly based and allow the diagnosis of SLE in patients with diverse clinical and serologic features. Most patients without anti-DNA antibodies do have antinuclear antibodies of other specificities (e.g., anti-Sm, anti-Ro, anti-La). It is possible, though we doubt it, that more sensitive assays would detect anti-DNA antibodies in all SLE patients. Thus on balance, lupus should really be considered a generic term, encompassing several individual conditions.The presence of anti-DNA antibodies in the serum of SLE patients has long been considered both a marker of, and pathologic factor in, renal disease (3,4). Indeed, in our group of nearly 200 SLE patients, we have yet to see a patient with severe renal involve-

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Immunoglobulin variable genes and epitope recognition of human monoclonal anti-Ro 52-kd in primary Sj�gren's syndrome

Elagib

Tengnér

Levi

et al. 1999

Arthritis & Rheumatism

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Objective. To clone and characterize human anti-Ro/SSA autoantibodies from a patient with primary Sjögren's syndrome (pSS). Methods. Monoclonal antibodies (mAb) were raised from the peripheral blood of a patient with pSS using Epstein-Barr virus transformation and a hybrid-oma technique. Specificity was determined using cell extracts, recombinant Ro 52-kd, Ro 60-kd, and La proteins as well as Ro 52-kd peptides in enzyme-linked immunosorbent assay (ELISA) and Western blot. The immunofluorescence pattern was analyzed using cultured human and mouse cell lines. Complementary DNA was amplified by polymerase chain reaction, and Ig variable (V)-region genes were directly sequenced. Results. Two human anti-Ro 52-kd mAb of IgM isotype, denoted SG1 and SG3, were cloned from the peripheral blood of a patient with pSS. The 2 mAb reacted with the Ro 52-kd antigen in cell extracts of human cell lines and mouse cell lines, and with purified human recombinant Ro 52-kd protein in ELISA and Western blot. SG1 reacted specifically with 1 peptide, amino acids 136-156, of the Ro 52-kd protein, and SG3 was mapped to react with a recombinant fragment representing amino acids 136-292. Immunofluores-cence studies revealed cytoplasmic staining with both mAb. Both were encoded by V H 3-family genes. SG1 was highly homologous to the DP-77 germ-line gene, with 2 replacement mutations and 1 silent. It utilized the DPL-11 germ-line gene from the V 2-family gene, with 1 silent mutation. SG3 was 100% homologous to the DP-47 germ-line gene, combined with a V 1-family gene that was 100% homologous to the A30 germ-line gene. Conclusion. Two human mAb were demonstrated to be specific for the Ro 52-kd protein and to be directed against 2 different epitopes, 1 linear and 1 con-formation-dependent, within a region previously described to be immunodominant. Somatic hypermutation appeared to be of minor importance in generating these 2 specificities.

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Characterization of human-human hybridoma monoclonal anti-Ro(SS-A) autoantibodies derived from normal tonsil lymphoid cells

Cited by 5 publications

References 41 publications

T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation

T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation

The Origin, Sequence, Structure, and Consequences of Developing Anti‐DNA Antibodies

Immunoglobulin variable genes and epitope recognition of human monoclonal anti-Ro 52-kd in primary Sj�gren's syndrome

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