The B-cell repertoire for autoantibodies: Frequency of precursor cells for anti-DNA antibodies

Abstract

To investigate the B-cell repertoire for autoantibodies, the frequency of precursor cells capable of expressing anti-DNA antibodies in normal and autoimmune mice was evaluated by in vitro limiting dilution analysis. Spleen cell preparations from BALB/c, CBA/J, and MRL- lpr/lpr mice were stimulated at graded cell numbers in microcultures with LPS at 50 μg/ml in the presence of rat thymus filler cells. Culture supernatants were then assayed for IgM antibodies by an enzyme-linked immunosorbent assay; anti-DNA was measured as a model autoantibody response while the anti-TNP hapten response was determined as a control for an ordinary antibody response. The conditions for cell activation were found to be the same for the two responses and both demonstrated high precursor cell frequencies. Approximately 1 in 500 spleen cells was found committed to each response with similar frequencies in normal and autoimmune strains. These results indicate an abundant representation of some anti-DNA antibodies among normal B cells, without apparent augmentation by the autoimmune state. However, since not all anti-DNA antibodies may be pathogenic, it remains uncertain that the composition and disease potential of the B-cell repertoires of normal and autoimmune mice are comparable.