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.