B cells influence sex specificity of arthritis via myeloid suppressors and chemokines in humanized mice

Clin Immunol. 2017 May:178:10-19. doi: 10.1016/j.clim.2015.05.015. Epub 2015 Jun 6.

Abstract

Rheumatoid arthritis (RA) occurs two times more often in women than men. B cell depletion has been shown to be efficacious in treating RA. Our previous studies suggested that antigen presentation via B cells results in a sex-specific immune response in DR4 and DR4/DQ8 mice. Here we evaluated the mechanism of efficacy of the B cell depletion in treating arthritis-susceptible DQ8 mice. The data show that arthritic DQ8 mice treated with anti-CD20 antibody in therapeutic protocols show milder disease severity in females as compared to males, which is associated with decreased antibodies to citrullinated proteins and reduced levels of IL-23 and CCL5. Treatment led to significantly increased numbers of T regulatory and monocyte-derived suppressor F4/80+Gr1hi cells in females as compared to male DQ8 mice. Our observations suggest that therapeutic strategies that target B cells may benefit females while functions of DCs might be relatively more important for men than women.

Keywords: Collagen-induced arthritis; Humanized mice; Myeloid suppressor cells; Rheumatoid arthritis; Rituximab; T regulatory.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology
  • Arthritis, Experimental / genetics
  • Arthritis, Experimental / immunology*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • CD28 Antigens / immunology
  • CD40 Antigens / immunology
  • Cell Proliferation
  • Chemokine CCL5 / drug effects
  • Chemokine CCL5 / immunology*
  • Chemokines / drug effects
  • Chemokines / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Female
  • Flow Cytometry
  • HLA-DQ beta-Chains / genetics
  • Humans
  • Interleukin-23 / drug effects
  • Interleukin-23 / immunology*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Transgenic
  • Myeloid-Derived Suppressor Cells / immunology*
  • Receptors, Antigen, T-Cell / immunology
  • Rituximab / pharmacology
  • Sex Characteristics
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Antirheumatic Agents
  • CD28 Antigens
  • CD40 Antigens
  • Chemokine CCL5
  • Chemokines
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Interleukin-23
  • Receptors, Antigen, T-Cell
  • Rituximab