Overlap of the anti-cardiolipin and anti-nucleosome responses of the (NZW X BXSB)F1 mouse strain: a new pattern of cross-reactivity for lupus-related autoantibodies.
The association of anti-nuclear antigen (ANA) and anti-cardiolipin (CL) antibodies is often observed during systemic lupus erythematosus (SLE) or the primary anti-phospholipid syndrome, thereby raising the possibility of a relationship between these two autoantibody populations. To determine whether ANA and anti-CL antibodies can overlap, we derived, from a male (NZW x BXSB)F1 mouse, 14 hybridomas selected based on their capacities to react with CL and to label HEp-2 cell nuclei. Four of these anti-CL were IgG and bound to CL and phosphatidylserine in a cofactor-dependent manner and reacted strongly with nucleosomes. Variable region sequence analysis indicated that these four monoclonal antibodies (mAb) were derived from three independent B cell clones that used recurrent heavy and/or light chain immunoglobulin rearrangements, as assessed by comparison with each other and prototypic anti-CL mAb previously derived from different lupus mouse strains. These results indicate that anti-CL mAb can have overlapping cross-reactivities with nucleosomes, thereby defining a new category of SLE-related autoantibodies characterized by their capacities to recognize distinct supramolecular complexes, formed by the association of an anionic structure and a protein, that exert a strong selective pressure on autoreactive B cell clones.
Gilbert
D
D
INSERM 519, Institut Fédératif de Recherche Multidisciplinaire sur les Peptides (IFR23), Faculté Mixte de Médecine et de Pharmacie, H opital Charles Nicolle, Rouen, France. Daniele.Gilbert@univ-rouen.fr
Lopez
B
B
Parain
J
J
Koutouzov
S
S
Tron
F
F
D000595:Amino Acid Sequence; D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D003429:Cross Reactions; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000276:immunology*
D017153:Antibodies, Anticardiolipin; D001323:Autoantibodies; D009707:Nucleosomes