April 3, 2013

“Silent” B cells trigger autoimmunity

Immune cells that recognize self antigens (e.g. insulin), but are functionally silent, can trigger autoimmune diseases such as diabetes.

Autoreactive B lymphocytes – immune cells that recognize “self” antigens – can join the repertoire of circulating B cells in a state of functional silence, called anergy. Anergy is a form of immune tolerance that keeps these cells in check: they fail to proliferate or produce antibodies. Their possible contribution to autoimmune disease is not clear.

Peggy Kendall, M.D., assistant professor of Medicine, and colleagues investigated the potential of anergic, autoreactive mouse B cells expressing anti-insulin B cell receptors to “present” antigen and activate T cells.

They report in the March 15 Journal of Immunology that anergic anti-insulin B cells capture and rapidly internalize insulin for processing and presentation. They show that anergic B cells activate both anti-insulin T cells from a mouse model of diabetes and naïve T cells not previously exposed to antigen. They also report that with low antigen exposure, anergic B cells are more efficient than naïve B cells in activating T cells.

The findings indicate that anergic, autoreactive B cells may promote autoimmune diseases, such as type 1 diabetes, by driving the activation and expansion of autoaggressive T cells via antigen presentation.

This research was supported by grants from the National Institutes of Health (DK084246, AI051448, DK070924, DK084568) and from the Juvenile Diabetes Research Foundation.