B cells as effectors and regulators of sex-biased arthritis

David Luckey, Kay Medina, Veena Taneja

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

B cells have been implicated both with pathogenic as well as protective capabilities in induction and regulation of autoimmune diseases. Rheumatoid arthritis (RA) is an autoimmune disease that occurs more often in women than men. A significant role of B cells as antibody producing and antigen-presenting cells has been demonstrated in RA. Predisposition to RA is associated with the presence of certain HLA class II alleles that share sequences with DRB1*0401. To determine the role of HLA genes and B cells in vivo, we have generated transgenic mice carrying HLA genes, DRB1*0401 and DQ8, known to be associated with susceptibility to RA. Humanized mice can be induced to develop arthritis that mimics human disease in clinical, histopathological and sex bias. Effect of hormones on immune cells and their function has been described in humans and mice and has been suggested to be the major reason for female bias of autoimmune diseases. An immune response to an antigen requires presentation by HLA molecules thus suggesting a critical role of MHC in combination with sex hormones in susceptibility to develop rheumatoid arthritis. Based on our observations, we hypothesize that modulation of B cells by estrogen, presentation of modified antigens by DR4 and production of antigen-specific B cell modulating cytokines leads to autoreactivity in females. These data suggest that considering patient's sex may be crucial in selecting the optimal treatment strategy. Humanized mice expressing RA susceptible and resistant haplotype provide a means to investigate mechanism sex-bias of arthritis and future strategies for therapy.

Original languageEnglish (US)
Pages (from-to)364-376
Number of pages13
JournalAutoimmunity
Volume45
Issue number5
DOIs
StatePublished - Aug 2012

Keywords

  • Antigen presentation
  • B regulatory cells
  • HLA transgenic mice
  • MHC polymorphism
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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