Failure to remove autoreactive Vbeta6+ T cells in Mls-1 newborn mice attributed to the delayed development of B cells...

Clonal deletion of autoreactive T cells in the thymus is one of the major mechanisms for establishing tolerance to self-antigens, and self-reactive T cells bearing Vbeta6 T-cell receptors are usually deleted before their maturation in Mls-1a mice. However, these T cells develop transiently in the neonatal thymus, and migrate to the periphery. In order to understand the mechanisms which permit these potentially auto-toxic T cells to generate, we investigated in vivo the physiological or functional properties of the elements involved, such as neonatal T cells, antigens and antigen-presenting cells (APC). Confirming the previous findings that each of these elements per se is already completed in function in neonates, we investigated the possibility of the absence or immaturity of particular APC with Mls antigens of their own products in the neonatal thymus. In the search for the cellular and histological changes occurring in the newborn thymus, we found that the elimination of Vbeta6+ T cells progressed in parallel with the development of thymic B cells. Involvement of B cells in purging the autoreactive T cells from the newborn thymus was shown by prevention of the deletion of Vbeta6+ T cells after the removal of B cells by the treatment of neonates with anti-immunoglobulin M antibodies. The restricted and stable expression of CD5 on the thymic B cells, but not on the splenic cells, suggests that these B cells are not postnatal immigrants from the periphery. Finally, it is concluded that the deficiency in the deletion of self-reactive T cells in the thymus of Mls-1a neonates is due to the delayed development of B cells.