In vitro production of an anti-DNA idiotype by lymphocytes of normal subjects and patients with systemic lupus erythematosus

We investigated whether normal B cells can synthesize antibodies with an idiotypic marker that occurs with high frequency in anti-DNA antibodies of patients with systemic lupus erythematosus (SLE). This idiotype, Id ^{16 6}, has been found in the serum of patients with active SLE and in monoclonal anti-DNA antibodies derived from unrelated patients with the disease. We found that cultured lymphocytes of all normal subjects tested produced Id ^{16 6} when stimulated by pokeweed mitogen (PWM). By contrast, lymphocytes from SLE patients produced Id ^{16 6} even without mitogenic stimulation, whether or not they were obtained from patients in remission or relapse. Relapsed patients' lymphocytes spontaneously produced the highest levels of Id ^{16 6} which was found in IgG and IgA, in addition to IgM. The majority of Id ^{16 6} produced by PWM-stimulated lymphocytes from either normal subjects or patients in remission did not bind to nucleic acid. In relapse, however, the nucleic acid-binding proportion of Id ^{16 6} rose substantially, indicating that the spontaneously activated B cells in active SLE differ from the subset of B cells that produce Id ^{16 6} upon PWM stimulation. The findings suggest that the lupus Id ^{16 6} family is conserved in normal individuals and it consists of two populations of antibodies with different antigenic specificities. The major set is not directed against nucleic acid antigens; its antigenic specificity is unknown and it dominates the Id ^{16 6} family that appears after PWM stimulation. The other, minor set binds to nucleic acids and becomes prominent in clinically active lupus. These two sets of idiotypically related antibodies may be connected by an immunoregulatory network.