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Gonadal steroids and humoral immunity

Nature Reviews Endocrinology volume 9, pages 56–62 (2013)Cite this article

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Abstract

Humoral immune responses are sexually dimorphic. Female individuals generally exhibit more-robust antibody responses to vaccines and, in the clinical setting as well as in experimental models, are more likely than male individuals to produce autoreactive antibodies of pathogenic potential. A number of differences between the sexes might account for these observations, including differences in the dosage of specific X-chromosome and Y-chromosomal genes, increased exposure of female individuals to antigenic stimulation in childbearing, and differences in circulating concentrations of gonadal steroid hormones. The role of gonadal steroids in modulating such humoral immune responses has been studied for nearly a century, but advances in our knowledge of B-lymphocyte development and function, the mechanisms of immune tolerance, and the molecular basis of gonadal steroid hormone action are now yielding new understanding of the influence of gonadal steroid hormones on the humoral immune system. This Review examines how oestrogens and androgens modulate B-lymphocyte development and function, focusing on the areas of B-cell production in the bone marrow, the maintenance of immune tolerance for self antigens, and the processes of immunoglobulin heavy chain gene somatic hypermutation and class switch recombination during maturation of cells involved in humoral immune responses.

Key Points

  • Humoral immune responses are sexually dimorphic: female individuals exhibit more-exuberant antibody responses to vaccines and have a greater propensity for autoantibody production than do male individuals

  • Gonadal steroids exert effects on the immune system that could account, at least in part, for the observed sex differences in immunity and the incidence of autoimmune diseases

  • Androgens and oestrogens attenuate global B-cell production; their effects are mediated both directly (by actions on lymphoid cell precursors) and indirectly (through actions on bone marrow stromal cells)

  • Oestrogens modulate clonal deletion, the process through which autoreactive clones of B cells are eliminated

  • Gonadal steroids exert effects on immunoglobulin heavy chain gene somatic hypermutation and class switch recombination by modulating expression of activation-induced cytidine deaminase, the key regulator of these processes

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Figure 1: B lymphopoiesis.
Figure 2: Elimination of autoreactive B lymphocytes.
Figure 3: B lymphocytes switch the class of the immunoglobulin that they express as a result of recombination events in IGH@.

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Acknowledgements

The authors express their appreciation to Dr Ann L. Benko for critical reading of the manuscript. The authors acknowledge research grant support (to W. J. Kovacs as principal investigator) from the Lupus Research Institute, New York, USA.

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes, and Metabolism, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, 17033–10850, PA, USA

    Sanaz Sakiani & William J. Kovacs

  2. Division of Rheumatology, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, 17033–10850, PA, USA

    Nancy J. Olsen

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All authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission.

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Correspondence to William J. Kovacs.

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Sakiani, S., Olsen, N. & Kovacs, W. Gonadal steroids and humoral immunity. Nat Rev Endocrinol 9, 56–62 (2013). https://doi.org/10.1038/nrendo.2012.206

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