Susceptibility to tolerance induction of bursal and peripheral B cells

We investigated cellular aspects of immunological tolerance to protein antigens in chickens by examining the immune responses of bursal and splenic cells from tolerant or normal chickens after transfer into cyclophosphamide (CP)-treated recipients. Newly-hatched chicks were made tolerant to bovine serum albumin (BSA) by injection of 100 mg of the antigen. When bursa cells from 4-day-old BSA-unresponsive chicks were transferred into CP-treated recipients, the reconstituted birds were able to respond to a subsequent injection of BSA almost as well as normal birds, and as well as CP-treated birds that had been reconstituted with normal bursa cells. To investigate whether the presence of the BSA antigen might affect recovery from tolerance, we injected CP-treated recipients with BSA at the time of transfer of bursal cells. The presence of the antigen prevented the recovery of the anti-BSA response in reconstituted birds. When spleen cells from 6.5-week-old unresponsive chicks were transferred into CP-treated recipients, no recovery of responsiveness to BSA could be demonstrated. A likely reason for the failure of splenic B cells to recover responsiveness on transfer is their inability to generate somatic variants of Ig genes in the same way as bursal stem cells. Thus, when the bursa involutes, the chicken's antibody repertoire may be frozen in a less adaptable state than that of a mammal.