Heavy-chain receptor editing unbound.

With all of the certainty of death and taxes, questions regarding the mechanisms of immunological tolerance remain fixtures across the landscape of immunology. From Paul Ehlirch’s “horror autotoxicus” (reviewed in ref. 1) to the current synthesis of tolerance by apoptosis, anergy, and receptor editing (2), the mechanisms of immunological tolerance remain, despite substantial research effort, enigmatic. In PNAS, Kumar et al. (3) and Sun et al. (4) refine our understanding of receptor editing, a principle component of immune tolerance, by demonstrating that at least one form of this tolerance pathway is not driven by reaction with self-antigens.