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.