Hoxb8 belongs to the homeobox transcription factor family. Hoxb8 knockout (KO) mice exhibit a compulsive grooming, similar to trichotillomania (an impulse control disease) in humans. Hoxb8 is expressed in multiple hematopoietic cells. Bone marrow (BM) cells from Hoxb8 KO are less competitive than wildtype (wt) BM cells in granulocyte/monocyte and T cell lineages, yet more competitive in B cell lineage. How these changes affect development and functions of lymphocytes remain unknown. Here we report that autoimmunity was developed in Hoxb8 KO. Hoxb8 KO sera contain autoantibody against several self-tissues, including brain, kidney and liver. Splenomegaly was found with a higher frequency in KO mice, associating with increased B and T cell numbers. The percentages of surface IgG+ B and activated T cells were significantly increased as well. Moreover, serum IgG levels showed an age-dependent increase: there were trends of increased IgG levels in 3 and 6 month old KO, compared to aged matched wt mice, but all IgG isotypes, except IgG3, were significantly increased in the 9-month-old KO mice. Finally, we showed that autoimmunity developed in Hoxb8 KO mice may not be the major cause of the excessive grooming behavior since compulsive grooming remains in Hoxb8/RAG2 double KO mice. This observation suggests that defects of Hoxb8 in the immune system may play a supportive but not a major role in the pathogenesis of compulsive behavior, which agrees with our microglia hypothesis.
- Copyright © 2013 by The American Association of Immunologists, Inc.