Figure 1.

Hypothesized interactions of killer B cells with other lymphocytes. Fas ligand (FasL) expression is constitutive on mouse spleen and lung CD5⁺IgM^high B cells, which have been shown to kill antigen-specific T_H cells in vitro. Co-activation of mouse B cells through CD40 and the IL-5 receptor led to proliferation of CD5⁺ B cells, increased surface expression of FasL and killer function, and production and release of IL-10. (A) Interactions of killer B cells with mucosal type 2 innate lymphoid cells (ILC2), or with chronically stimulated T_H2 cells in vivo would be expected to support their growth and functions, but has not been formally proven. (B) Surface immunoglobulins on CD5⁺ B cells are poly-reactive and are known to recognize autoantigens that once bound can be internalized and processed into peptides, which are then presented to T_H cells on class II major histocompatibility (MHCII) molecules. (C) Binding of an autoantigen simultaneously by a killer B cell and an effector B cell could be a mechanism to explain B-cell fratricide, which has been described in several reports. (D) Killer B-cell uptake and presentation of autoantigens to T_H cells in the context of FasL–Fas signaling in vivo could lead to activation-induced cell death and is hypothesized to be an important mechanism for maintaining peripheral tolerance and preventing autoimmune diseases. These processes may also play a role in tolerance to food antigens, other allergens, and commensal microbes.