IgD BCR-mediated signals do not have protective roles in negative selection of autoreactive B cells in lpr mice

Abstract IgD is the major antigen receptor isotype coexpressed with IgM on the surface of most peripheral B cells in mice and humans. However, the biological role of IgD as B cell receptor (BCR) has remained enigmatic and controversial. Previous studies have indicated that IgD may play a role in B cell tolerance and the expression of IgD may rescue cells undergo programmed cell death. To understand the role of IgD in B cell tolerance and autoimmunity, we have examined the development of autoimmune syndrome in lpr mice deficient for IgD. The present study showed that IgD deficiency did not alter many aspects of the autoimmunity in lpr mice such as splenomegaly and significant expansion of activated T cells. Interestingly, lpr mice with IgD deficiency exhibited increased levels of autoantibodies and more severe nephritis compared to their IgD-competent littermates. In addition, the absence of IgD did not result in any increase in cell death of B cell subsets including transitional B cells. Thus, our results indicated that IgD BCR-mediated signals do not have a protective role in negative selection of autoreactive B cell clones. In contrast, the absence of IgD leads to heightened autoantibody production and more deposition of immune complex in the kidney, resulting in more severe nephritis.