This study investigates the role of B cells in preventing arthritis by producing interleukin (IL)-10. The researchers found that activating arthritogenic splenocytes with antigen and agonistic anti-CD40 leads to the generation of B cells that produce high levels of IL-10 and low levels of interferon (IFN)-γ. Transferring these B cells into DBA/1-TcR-β-Tg mice immunized with bovine collagen (CII) emulsified in complete Freund’s adjuvant inhibited T helper type 1 (Th1) differentiation and prevented arthritis development. IL-10 is essential for the regulatory function of these B cells, as B cells from IL-10 knockout mice failed to mediate this protective effect. Additionally, B cells isolated from arthritogenic splenocytes treated in vitro with anti-IL-10/anti-IL-10R were unable to protect recipient mice from developing arthritis. The results suggest a new role for a subset of B cells in controlling T cell differentiation and autoimmune disorders.This study investigates the role of B cells in preventing arthritis by producing interleukin (IL)-10. The researchers found that activating arthritogenic splenocytes with antigen and agonistic anti-CD40 leads to the generation of B cells that produce high levels of IL-10 and low levels of interferon (IFN)-γ. Transferring these B cells into DBA/1-TcR-β-Tg mice immunized with bovine collagen (CII) emulsified in complete Freund’s adjuvant inhibited T helper type 1 (Th1) differentiation and prevented arthritis development. IL-10 is essential for the regulatory function of these B cells, as B cells from IL-10 knockout mice failed to mediate this protective effect. Additionally, B cells isolated from arthritogenic splenocytes treated in vitro with anti-IL-10/anti-IL-10R were unable to protect recipient mice from developing arthritis. The results suggest a new role for a subset of B cells in controlling T cell differentiation and autoimmune disorders.