Autoantibody production is associated with polyclonal B cell activation in autoimmune mice which express the lpr or...

Systemic autoimmune disease in humans and mice is characterized by hypergammaglobulinemia and abnormally high levels of serum autoantibodies. The presence of certain genes, such as the lpr and gld genes, induces otherwise normal mice to spontaneously develop systemic autoimmunity. To better understand the effect of these genes on the development of hypergammaglobulinemia, we quantitated the absolute number of splenic B cells producing antibodies reactive with each of four autoantigens and two conventional antigens and compared this to the total number of Ig-secreting spleen cells present in these mice. Whereas autoimmune mice had significantly greater numbers of autoantibody-secreting spleen cells than normal mice, they also had significantly greater numbers producing antibodies of conventional specificity. When expressed as a proportion of the total repertoire, no bias towards autoantibody production was present when autoimmune lpr and gld animals were compared to their congenic nonautoimmune C57BL/6 and C3H/HeJ counterparts. We also examined the B cell repertoires of recombinant inbred mice derived by mating autoimmune NZB with normal NFS mice. Some recombinant inbred (RI) lines developed hypergammaglobulinemia and produced large quantities of autoantibody. While evidence for specific (auto)antigenic stimulation was present in some RI lines, hypergammaglobulinemia was commonly associated with polyclonal B cell activation in these autoimmune mice as well.