Characterization of a human monoclonal autoantibody directed to cardiolipin/β2 glycoprotein I produced by chronic lymphocytic leukaemia B cells

  title={Characterization of a human monoclonal autoantibody directed to cardiolipin/$\beta$2 glycoprotein I produced by chronic lymphocytic leukaemia B cells},
  author={Xavier Mariette and Yves L{\'e}vy and M L Dubreuil and Liliane Intrator and Françoise Danon and Jean Claude Brouet},
  journal={Clinical \& Experimental Immunology},
We determined the specificity and sequence of immunoglobulin molecules synthesized by monoclonal B cells from a patient with chronic lymphocytic leukaemia (CLL) who presented with a number of clinical and biological autoimmune symptoms. Helerohybrids obtained by fusion of CLL cells with the mouse X63‐Ag 8.653 myeloma produced IgMλ MoAbs directed to the cardiolipin/β2 glycoprotein I (β2GPI) complex and ssDNA. They were devoid of polyreactivity. Nuclcotide sequence analysis of the variable domain… 

Immunoglobulin gene sequence analysis of anti-cardiolipin and anti-cardiolipin idiotype (H3) human monoclonal antibodies.

Gene sequences which encode the disease-associated H3 idiotype and its location on lambda light chains, which imply that some labda light chains may be preferentially utilized in auto-reactive hybridomas, are shown.

Isolation and characterization of two human monoclonal anti-phospholipid IgG from patients with autoimmune disease.

Analysis of the heavy chain mRNA of HL-5B and RR-7F showed that both are members of the VH3 family, and both monoclonal APA can be used as tools in further structural and functional analyses.

The production, binding characteristics and sequence analysis of four human IgG monoclonal antiphospholipid antibodies.

Four human monoclonal IgG APL are developed by fusing the peripheral blood lymphocytes of three patients with SLE with a mouse human heteromyeloma cell line, CB-F7 and this supports the theory that clonal expansion is the mechanism whereby antigen selects high affinity mutations.

Lessons from Sequence Analysis of Monoclonal Antiphospholipid Antibodies

The hypothesis is that the Arg, Asn, and Lys residues increase the affinity of binding via electrostatic interactions and hydrogen bonds with negatively charged epitopes upon PL and domain I of β2-GPI, and thereby improve the treatment of APS.

An investigation of the importance of somatic mutations and basic residues in the binding of antiphospholipid antibodies to cardiolipin.

It was concluded that it is not just the presence but precise locations of specific arginine residues in the CDRs of pathogenic aPL, which are important in determining binding affinity for CL.

The clonal analysis of anticardiolipin antibodies in a single patient with primary antiphospholipid syndrome reveals an extreme antibody heterogeneity.

Clonal analysis of the reactivity of each one antibody making up the polyclonal anticardiolipin activity reveals the extreme heterogeneity of these antibodies, which could account for the difficulties in the previous attempts to define the pathogenic antiphospholipid response.

A systematic analysis of sequences of human antiphospholipid and anti-beta2-glycoprotein I antibodies: the importance of somatic mutations and certain sequence motifs.

An understanding of the role of arginine, asparagine, and lysine residues in the binding of pathogenic aPL to phospholipids, and to beta(2)-glycoprotein I, may eventually help in the development of drugs to interfere with those interactions, and thereby improve the treatment of antiphospholipid antibody syndrome.

Molecular properties of human monoclonal anti-DNA and antiphospholipid antibodies.

Analysis of the sequences of monoclonal anti-dsDNA and APL derived from humans or mice suggests that these binding properties are derived by antigen driven accumulation of mutations in the complementarity determining regions (CDRs) of the heavy and Ight chains.

Examining the non-linear relationship between monoclonal antiphospholipid antibody sequence, structure and function

This review will focus upon the sequence motifs that have been found to distinguish pathogenic from non-pathogenic aPL, and whether these or other properties may help to identify distinct pathogenic subsets of aPL.



A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene.

It is suggested that in SLE patients a common antigenic stimulus may evoke anti-DNA and anti-cardiolipin autoantibodies and provide further evidence that a small set of developmentally restricted VH genes can give rise to disease-associated autoantibia through Ag-selected somatic mutations.

A human anti-cardiolipin autoantibody is encoded by developementally restricted heavy and light chain variable region genes.

It is reported that the heavy and light chain V genes of an anti-cardiolipin antibody derived from a healthy individual display 99% nucleotide sequence homology with V genes expressed in early B cell ontogeny.

Autoantibody-associated kappa light chain variable region gene expressed in chronic lymphocytic leukemia with little or no somatic mutation. Implications for etiology and immunotherapy

It is proposed that many CLL cases represent malignancies of autoreactive CD5 B cells that use a restricted set of conserved V genes, which may render CLL particularly amenable to immunotherapy with antiidiotypic antibodies.

Nucleotide sequence analysis of the VL and VH domains of five human IgM directed to lamin B. Evidence for an antigen-driven process in the generation of human autoantibodies to lamin B.

The nucleotide sequence of the light and heavy chain variable region (VL and VH) domains of 5 IgM antibodies directed to lamin B are determined to provide evidence that the repertoire of human antilamin autoantibodies is not restricted and that the antigen plays a role in the generation of autoantibia.

Identification and sequence of the VH gene elements encoding a human anti-DNA antibody.

Comparison with the limited sequence data of published SLE monoclonal anti-DNA antibodies suggests that this shared Ser-Tyr may be important in some but not all antibodies to DNA.

Relationship of human variable region heavy chain germ-line genes to genes encoding anti-DNA autoantibodies.

The findings indicate that some SLE autoantibodies are encoded by unmodified or scarcely modified VH germ-line genes that are conserved in the human population and identify two distinct Vh germ- line genes that can encode segments of anti-DNA immunoglobulins.

A new human immunoglobulin VH family preferentially rearranged in immature B-cell tumours

Three germ-line VH gene segments are cloned and sequenced that constitute a new human VH family (subgroup V) linked within 160 kilobase pairs of the DH-JH complex, suggesting that biased rearrangement of subgroup V may be under developmental selection.

Analysis of immunoglobulin variable region genes from human IgG anti‐DNA hybridomas

Several VH and VL genes used by the hybridomas were found to be expressed in the natural antibody repertoire, in the restricted fetal repertoire and in B cell malignancies expressing the CD5 antigen.

Genetic analysis of self-associating immunoglobulin G rheumatoid factors from two rheumatoid synovia implicates an antigen-driven response

The results suggest strongly that the L1 IgG RF must have been driven by the Fc antigen, and suggests that at least part of the "potential pathogenic" IgGRFs in rheumatoid synovium may derive from the "physiological" natural antibody repertoire in a normal immune system.

Autoantibodies encoded by the most Jh-proximal human immunoglobulin heavy chain variable region gene

It is demonstrated that human antibodies with Ig VH regions encoded by the most JH-proximal human VH segment (VH6) have specificities resembling those of autoantibodies present in sera of patients with systemic lupus erythematosus.