title: B cells influence sex specificity of arthritis via myeloid suppressors and chemokines in humanized mice.
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+Gr1hicells 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.
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Marshall
authors.initials: M
authors.lastname: Behrens
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, USA.
authors.forename: David
authors.initials: D
authors.lastname: Luckey
authors.affiliation: Department of Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Harvinder
authors.initials: H
authors.lastname: Luthra
authors.affiliation: Department of Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Chella
authors.initials: C
authors.lastname: David
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, USA; Department of Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN, USA. Electronic address: taneja.vena@mayo.edu.
authors.forename: Veena
authors.initials: V
authors.lastname: Taneja
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D049109:Cell Proliferation; D018946:Chemokine CCL5 / Q000187:drug effects / Q000276:immunology*; D018925:Chemokines / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D059866:HLA-DQ beta-Chains / Q000235:genetics; D006801:Humans; D053759:Interleukin-23 / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D000069283:Rituximab / Q000494:pharmacology; D012727:Sex Characteristics; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: D018501:Antirheumatic Agents; D018106:CD28 Antigens; D019013:CD40 Antigens; D018946:Chemokine CCL5; D018925:Chemokines; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D053759:Interleukin-23; D011948:Receptors, Antigen, T-Cell; D000069283:Rituximab
keywords: Collagen-induced arthritis; Humanized mice; Myeloid suppressor cells; Rheumatoid arthritis; Rituximab; T regulatory