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

•Rituximab treatment is much more efficacious in females compared to males in advanced stages of disease.•Myeloid suppressor cells, T regulatory cells, and CCL5 are involved in protection from arthritis after Rituximab treatment.•B cell depletion does not suppress TCR-dependent response.•The study highlights a need for sex-specific treatment strategies for rheumatoid arthritis.

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.