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Intrinsic autoimmune capacities of hematopoietic cells from female New Zealand hybrid mice

Genes & Immunity volume 15, pages 153–161 (2014)Cite this article

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Abstract

Most systemic autoimmune diseases occur more frequently in females than in males. This is particularly evident in Sjögren’s syndrome, systemic lupus erythromatosis (SLE) and thyroid autoimmunity, where the ratio of females to males ranges from 20:1 to 8:1. Our understanding of the etiology of SLE implies important roles for genetics, environmental factors and sex hormones, but the relative significance of each remains unknown. Using the New Zealand hybrid mouse model system of SLE, we present here a new fetal liver chimera-based system in which we can segregate effects of immune system genes from that of sex hormones in vivo. We show that female hematopoietic cells express an intrinsic capacity to drive lupus-like disease in both male and female recipient mice, suggesting that this capacity is hormone independent. Particularly, only chimeric mice with a female hematopoietic system showed significantly increased numbers of germinal center B cells, memory B cells and plasma cells followed by a spontaneous loss of tolerance to nuclear components and hence elevated serum antinuclear autoantibodies. A protective effect of testosterone was noted with regard to disease onset, but not disease incidence. Thus, genetic factors encoded within the female hematopoietic system can effectively drive lupus-like disease even in male recipients.

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Acknowledgements

We thank Shirley Sobus and Joshua Loomis for their help with flow cytometric experiments. This study was supported in part by the Denver Autoimmune Center of Excellence and USPHS Grants AI18785 and AI22295 (to PM) and by R21AI083804 (to TNJ).

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Author notes

  1. M K MacLeod

    Present address: 3Current address: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow, UK.,

  2. A C Johnson

    Present address: 4Current address: Department of Biology, Notre Dame College, 4545 College Road, South Euclid, OH, USA.,

Authors and Affiliations

  1. Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Health, Denver, CO, USA

    A David, M K MacLeod, P Marrack & T N Jørgensen

  2. Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

    A Trigunaite, A C Johnson & T N Jørgensen

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  1. A David
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Correspondence to T N Jørgensen.

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David, A., Trigunaite, A., MacLeod, M. et al. Intrinsic autoimmune capacities of hematopoietic cells from female New Zealand hybrid mice. Genes Immun 15, 153–161 (2014). https://doi.org/10.1038/gene.2014.2

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