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.

A defining feature of Ig Tg sHEL mice is the paucity of anti-HEL auto-Ab production. To examine EndoU function in this process, EndoU / Ig Tg sHEL mice were generated. Serum anti-HEL auto-Ab levels were strikingly high in some EndoU / Ig Tg sHEL mice, which were labeled "high responders" (Fig. 6 A) . Anti-HEL auto-Ab levels in high-responder EndoU / Ig Tg sHEL mice were even greater than the levels of spontaneous anti-HEL Ab produced in Ig Tg mice (1.9-fold increase, P = 0.02) and EndoU / Ig Tg mice (1.8-fold increase, P < 0.01) lacking auto-Ag. High-responder EndoU / Ig Tg sHEL mice were present in both sexes, and carried both the Ig Tg and sHEL transgenes (Fig. 6 B) . High serum anti-HEL auto-Ab levels developed in most high-responder mice after 5 wk of age and were maximal by 9-12 wk of age (Fig. 6 , A and C). In addition to high-responder EndoU / Ig Tg sHEL mice, their age-matched littermates had augmented anti-HEL auto-Ab levels that were 2.4-fold higher than Ig Tg sHEL mice (P = 0.01, Fig. 6 A) . Anti-HEL auto-Ab levels in augmented-responder mice continued to increase with age ( Fig. 6 D) , whereas anti-HEL auto-Abs were not enhanced in old Ig Tg sHEL mice (not depicted). Thus, EndoU overexpression regulates B cell auto-Ag responses in Ig Tg sHEL mice.