The secret autoreactivity of B cells

Like the proverbial wolf in sheep's clothing, B cells can hide the fact that they are harboring a dangerous autoreactive immunoglobulin (Ig) by displaying a second innocuous Ig. Casellas et al. (page 153) now reveal how these fluffy white villains come to exist and, rather worryingly, that there are potentially large numbers of them in our system.

Transgenic B cells forced to express one self-reactive Ig allele can switch on a second nonautoreative Ig in a process called allelic inclusion. This second Ig appears to dilute the autoreactive potential of the cell. But it is unknown whether allelic inclusion, which defies the “one lymphocyte–one antibody” theory of B cell specificity, can occur under normal physiological conditions.

Using physiologically normal mice that carried one human and one endogenous...