Acquired Autoantibodies from Human Plasma B Cells by Light Chain Shifting

Abstract

HTD8 is one of concanavalin A-resistant variant subclones of a human plasma B cell line. We have shown that HTD8 expresses various new light chains replacing the original light chain at a high rate. This process of replacing the original light chain in antibody secreting cells was called “light chain shifting”. The subclones of transformed-HTD8 cells by introducing certain human antibody heavy chain gene, expressed new light chains which led to altered antigen binding in both specificity and affinity. These results raise the possibility that plasma B cell can be altered to be generate autoantibodies. We examined this possibility by assessing an autoantigens binding of hybrid antibody molecules from the transformed-HTD8 cells repertoire. The hybrid antibodies were obtained by panning against dsDNA and further examined with other autoantigens. Some of the antibodies produced from the transformed-HTD8 cells also express a different light chain and shown to be of high affinity with double-stranded DNA (dsDNA), human thyroglobulin, and Fc fragment of human IgG. These results indicated that light chain shifting can be utilized to generated autoantibodies with high affinity and polyspecificity to various autoantigens by an antibody having no significant affinity for autoantigens.