EndoU is a novel regulator of AICD during peripheral B cell selection

Poe, Jonathan C.; Kountikov, Evgueni I.; Lykken, Jacquelyn M.; Natarajan, Abirami; Marchuk, Douglas A.; Tedder, Thomas F.

EndoU overexpression in vivo also occurred in response to BCR signals generated in Ig Tg sHEL mice, where B cells displayed a CD5 high HSA high IgM low phenotype and failed to up-regulate c-Myc expression as was observed in CD22 /[B6] mice. Genetic deletion of EndoU normalized this B cell phenotype in a substantial number of Ig Tg sHEL mice, which correlated with robust anti-HEL auto-Ab responses at an early age in mice that were defined as high responders. In augmented-responder EndoU / Ig Tg sHEL mice, some B cells expressed normalized phenotypes, suggesting that some B cells escape from an AICD phenotype with age to generate higher anti-HEL auto-Ab levels than Ig Tg sHEL mice. Given the linkage between EndoU, c-Myc up-regulation and AICD, it is likely that decreased B cell AICD in EndoU / Ig Tg sHEL mice leads to increased numbers of B cells that eventually consume endogenous sHEL auto-Ag, permitting clonal expansion with a resultant increase in anti-HEL auto-Ab production.