Sex and systemic lupus erythematosus: the role of the sex hormones estrogen and prolactin on the regulation of autoreactive B cells

Curr Opin Rheumatol. 2006 Sep;18(5):456-61. doi: 10.1097/01.bor.0000240354.37927.dd.


Purpose of review: For many decades, it has been speculated that sex hormones play a role in systemic lupus erythematosus. Recent data accumulated during the past few years provide striking evidence that hormonal modulation of B cells can have a profound impact on the survival, maturation and repertoire selection of autoreactive B cells and begin to explain the sex bias associated with the condition.

Recent findings: While there are still insufficient clinical data to define a role for estrogen or prolactin in human systemic lupus erythematosus, recent studies of anti-DNA antibody transgenic mice clearly demonstrate that an elevation in either estrogen or prolactin breaks tolerance of high affinity DNA-reactive B cells and induces a lupus phenotype. B cells with the same antigenic specificities are rescued by either estrogen or prolactin, but estrogen promotes the survival and activation of the T independent marginal zone B cell subset, while prolactin promotes the survival and activation of the T dependent follicular B cell subset.

Summary: Elevations in the levels of estrogen or prolactin can promote the survival and activation of high affinity autoreactive B cells. These hormones engage different B cell pathways to interfere with B cell tolerance. The identification of systemic lupus erythematosus patients with either an estrogen-responsive or prolactin-responsive disease will further the development of therapeutics that can specifically modulate hormonal responses.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Antinuclear / genetics
  • Antibodies, Antinuclear / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Cell Survival / immunology
  • Estrogens / immunology*
  • Female
  • Humans
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / pathology
  • Lupus Erythematosus, Systemic / therapy
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Transgenic
  • Prolactin / immunology*
  • Self Tolerance / genetics
  • Self Tolerance / immunology*
  • Sex Characteristics*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology


  • Antibodies, Antinuclear
  • Estrogens
  • Prolactin