Role of Nr13 in regulation of programmed cell death in the bursa of Fabricius

Apoptotic cell death is developmentally regulated in the chicken bursa of F abridus. Although apoptosis is low in the embryonic bursa, cell death incre ases markedly after hatching. The expression of Bcl2 family cell death anta gonists was examined to identify the genes that regulate bursal:ell apoptos is. The expression of Bcl-xL, Al, and Mcl1 was detected in bath embryos and hatched birds, whereas Nr13 was expressed at high levels in embryonic burs a, and decreased significantly after hatching, correlating inversely with! apoptosis. The oncogene v-reland phorbol myristate acetate, two known inhib itors of bursal cell apoptosis, induced Nr13 expression. Overexpression of Nr13 in DT40 bursal lymphoma cells protected them from low serum-induced ap optosis. The mechanism of inhibition of apoptosis by Nr13 is likely to invo lve a critical BH4 domain and interaction with death agonist Bar, Deletion of the BH4 domain converted Nr13 into a death agonist. Bar coimmunoprecipit ated with Nr13 and fax tvas induced, whereas Nr13 levels diminished when bu rsal lymphoblasts were induced to apoptosis by dispersion. Bursal transplan tation studies demonstrated that Nr13 could prevent the in vivo programmed elimination of bursal stem cells after hatching, suggesting that Nr13 plays a role in maintaining bursal stem cells.