title: Sex and systemic lupus erythematosus: the role of the sex hormones estrogen and prolactin on the regulation of autoreactive B cells.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Columbia University, 1130 St. Nicholas Avenue, New York, NY 10032, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Grimaldi
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002470:Cell Survival / Q000276:immunology; D004967:Estrogens / Q000276:immunology*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011388:Prolactin / Q000276:immunology*; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology*; D012727:Sex Characteristics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D004967:Estrogens; D011388:Prolactin