This study demonstrates that activation of arthritogenic splenocytes with antigen and agonistic anti-CD40 mAb leads to a B cell population that produces high levels of IL-10 and low levels of IFN-γ. Transfer of these B cells into DBA/1-TcR-β-Tg mice immunized with bovine collagen (CII) emulsified in complete Freund's adjuvant inhibits T helper type 1 (Th1) differentiation, prevents arthritis development, and ameliorates established disease. IL-10 is essential for the regulatory function of these B cells, as B cells from IL-10 knockout mice fail to mediate this protective function. The study also shows that B cells isolated from arthritogenic splenocytes treated with anti-IL-10/anti-IL-10R are unable to protect recipient mice from arthritis. These results suggest a new role for a subset of B cells in controlling T cell differentiation and autoimmune disorders. The study highlights the importance of IL-10 in the regulatory function of B cells, which can suppress Th1 responses and reduce inflammation in autoimmune diseases. The findings indicate that B cells, when activated by anti-CD40, can produce IL-10 and contribute to the regulation of immune responses, offering a potential therapeutic approach for autoimmune diseases such as rheumatoid arthritis.This study demonstrates that activation of arthritogenic splenocytes with antigen and agonistic anti-CD40 mAb leads to a B cell population that produces high levels of IL-10 and low levels of IFN-γ. Transfer of these B cells into DBA/1-TcR-β-Tg mice immunized with bovine collagen (CII) emulsified in complete Freund's adjuvant inhibits T helper type 1 (Th1) differentiation, prevents arthritis development, and ameliorates established disease. IL-10 is essential for the regulatory function of these B cells, as B cells from IL-10 knockout mice fail to mediate this protective function. The study also shows that B cells isolated from arthritogenic splenocytes treated with anti-IL-10/anti-IL-10R are unable to protect recipient mice from arthritis. These results suggest a new role for a subset of B cells in controlling T cell differentiation and autoimmune disorders. The study highlights the importance of IL-10 in the regulatory function of B cells, which can suppress Th1 responses and reduce inflammation in autoimmune diseases. The findings indicate that B cells, when activated by anti-CD40, can produce IL-10 and contribute to the regulation of immune responses, offering a potential therapeutic approach for autoimmune diseases such as rheumatoid arthritis.