Monoclonal autoantibodies to histones from autoimmune NZB/NZW F₁ mice

Fusion of spleen cells from autoimmune NZB/NZW female mice with drug‐resistant myeloma cells (clones NSI/1, X63‐Ag8.653 and NSO/1) produced hybrid clones which secreted antibodies to various nuclear components. Roughly 50% of the anti‐nuclear hybridomas produced antibodies reacting with DNA, 20% with RNA and 30% reacted with other nuclear antigens. Two hybridomas of the latter group were cloned and studied in detail. They secreted antibodies which produced bright fluorescence staining of nuclei and metaphase chromosomes. The specificity of the antibodies was determined by testing them in an enzyme‐linked immunosorbent assay and a radioimmunoassay against individual acid‐ and salt‐extracted histones, against histones mixed two and three at a time and against histone complexes isolated as such from chromatin. One of the monoclonal antibodies was specific for histone H2B and reacted with the histone free in solution or when present as a H2A‐H2B complex. The second monoclonal antibody recognized a specific conformation in the H3‐H4 complex that was present only when the complex was obtained from chromatin by salt extraction. The same conformation, however, could be induced by adding histone H2B to a mixture of acid‐extracted H3 and H4. Our findings show that the autoimmune syndrome in NZB/NZW mice resembles human systemic lupus erythematosus not only in the incidence of antibodies to DNA and RNA, but also in the production of autoantibodies to histones.