Peripheral B cell receptor editing may promote the production of high‐affinity autoantibodies in CD22‐deficient mice

CD22‐deficient mice are characterized by B cell hyperactivity and autoimmunity. We have constructed knock‐in CD22–/– mice, expressing an anti‐DNA heavy (H) chain (D42), alone or combined with Vκ1‐Jκ1 or Vκ8‐Jκ5 light (L) chains. The Ig‐targeted mice produced a lupus‐like serology that was age‐ and sex‐dependent. High‐affinity IgG autoantibodies were largely dependent on the selection of B cells with a particular H/L combination, in which a non‐transgenic, endogenous L chain was assembled by secondary rearrangements through the mechanism of receptor editing. Moreover, we present evidence that these secondary rearrangements are very prominent in splenic peripheral B cells. Since CD22 is primarily expressed on the surface of peripheral B cells, we propose a model for the development of a lupus‐like autoimmune disease by a combination of peripheral receptor editing and abnormal B cell activation.