Killer B lymphocytes: the evidence and the potential

Abstract

Immune regulation plays a critical role in controlling potentially dangerous inflammation and maintaining health. The Fas ligand/Fas receptor axis has been studied extensively as a mechanism of killing T cells and other cells during infections, autoimmunity, and cancer. FasL expression has been primarily attributed to activated T cells and NK cells. Evidence has emerged that B lymphocytes can express FasL and other death-inducing ligands, and can mediate cell death under many circumstances. Among B cell subsets, the expression of both Fas ligand and IL-10 is highest on the CD5(+) B cell population, suggesting that CD5(+) B cells may have a specialized regulatory function. The relevance of killer B cells to normal immune regulation, disease pathogenesis, and inflammation is discussed.

Fig. 1

A model showing the possible duality in roles of a single autoreactive B cell during the regulation or promotion of autoimmunity. Self antigen recognition by an autoreactive B cell receptor leads to activation of a killer/regulatory or stimulatory B cell depending on the secondary signals received concurrently. LPS and factors promoting a Th2 effector phenotype may favor production of killer/regulatory B cells, while factors that promote a Th1 or Th17 phenotype may favor a stimulatory B cell phenotype. Killer/regulatory B cells producing IL-10, TGFβ, FasL, and/or other death-inducing ligands may interact with an autoreactive T cell leading to induction of tolerance. Stimulatory B cells producing IL-6, TGFβ, upregulated B7 molecules, and/or decreased death ligand expression may interact with autoreactive T cells leading to induction of IL-17 and promotion of autoimmunity. It remains unclear whether a single autoreactive B cell can be forced into either one of these roles, or whether regulatory and stimulatory autoreactive B cells come from separate B cell compartments