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

Publication date: May 2017
Source:Clinical Immunology, Volume 178
Author(s): Marshall Behrens, David Luckey, Harvinder Luthra, Chella David, Veena Taneja
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+Gr1^hi 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.



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