To assess the importance of B cell control of T cell differentiation, we analyzed the course of the T helper type 1 (T(H)1)-driven disease experimental autoimmune encephalomyelitis in mice with an altered B cell compartment. We found that recovery was dependent on the presence of autoantigen-reactive B cells. B cells from recovered mice produced interleukin 10 (IL-10) in response to autoantigen. With a bone marrow chimeric system, we generated mice in which IL-10 deficiency was restricted to B cells but not T cells. In the absence of IL-10 production by B cells, the pro-inflammatory type 1 immune response persisted and mice did not recover. These data show that B cell-derived IL-10 plays a key role in controlling autoimmunity.

The immune system can remember, sometimes for a lifetime, the identity of a pathogen. Understanding how this is accomplished has fascinated immunologists and microbiologists for many years, but there is still considerable debate regarding the mechanisms by which long-term immunity is maintained. Some of the controversy stems from a failure to distinguish between effector and memory cells and to define their roles in conferring protection against disease. Here the current understanding of the cellular basis of immune memory is reviewed and the relative contributions made to protective immunity by memory and effector T and B cells are examined.

In this study we have shown that activation of arthritogenic splenocytes with antigen and agonistic anti-CD40 gives raise to a B cell population that produce high levels of interleukin (IL)-10 and low levels of interferon (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 inhibited T helper type 1 differentiation, prevented arthritis development, and was also effective in ameliorating established disease. IL-10 is essential for the regulatory function of this subset of B cells, as the B cells population isolated from IL-10 knockout mice failed to mediate this protective function. Furthermore, 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. Our results suggest a new role of a subset of B cells in controlling T cell differentiation and autoimmune disorders.

IL-6–producing B cells contribute to EAE pathology and possibly human MS, whereas ablation of B cell IL-6 is associated with a reduced Th17 response.