Natural and Pathological Autoantibodies Show Age-Related Changes in a Spontaneous Autoimmune Mouse (NZB) Model

The natural autoantibody (natAAb) network is thought to play a role in immune regulation. These IgM antibodies react with evolutionary conserved antigens; however, they do not lead to pathological tissue destruction as opposed to pathological autoantibodies (pathAAb). The exact relation between the natAAbs and pathAAbs is still not completely understood; therefore, in the present study, we set out to measure nat- and pathAAb levels against three conserved antigens in a spontaneous autoimmune disease model: the NZB mouse strain which develops autoimmune hemolytic anemia (AIHA) from six months of age. There was an age dependent increase in the natAAb levels in the serum against Hsp60, Hsp70, and the mitochondrial citrate synthase until 6-9 months of age, followed by a gradual decrease. The pathological autoantibodies appeared after six months of age, which corresponded with the appearance of the autoimmune disease. The changes in nat/pathAAb levels were coupled with decreasing B1- and increasing plasma cell and memory B cell percentages. Based on this, we propose that there is a switch from natAAbs towards pathAAbs in aged NZB mice.

Automated summary

The natural autoantibody (natAAb) network plays a role in immune regulation by reacting with evolutionary conserved antigens without causing tissue destruction. The relation between natAAbs and pathAAbs is not completely understood. In this study, the levels of nat- and pathAAb against three conserved antigens were measured in NZB mice, a spontaneous autoimmune disease model. The levels of natAAbs increased until 6-9 months of age and then decreased, while pathAAbs appeared after six months of age, corresponding with the onset of autoimmune disease. The changes in nat/pathAAb levels were associated with alterations in B1 cells, plasma cells, and memory B cells, suggesting a switch from natAAbs towards pathAAbs in aged NZB mice.