We discuss how perturbations, like an infection with foreign antigen, a change in the influx of new idiotypes, or the random removal of idiotypes, may lead to autoreactivity and devise protocols which cause a reconstitution of the self-tolerant state.
Mature self-tolerant thymocytes leave the thymus for the periphery near the cortico-medullary junction.
Through positive and negative selection, an immunocompetent and self-tolerant T cell repertoire is generated [7], [8].
Consequently, agnathans are thought to generate a self-tolerant immune repertoire through the evolutionary selection for non-autoreactive receptor building blocks [23].
As regulation of plasma cell differentiation for self-tolerant B lymphocytes occurs at the transition from the early to late pre-plasma cell stage [24], we examined these cell populations in NZB dTg mice.
However, recent evidence show that up to 20% of the peripheral blood NK cells may be KIR-negative, yet self-tolerant, as these cells probably reflect an immature stage [8] [10].
ClinicalTrials.gov NTC00601419 The thymus is the unique lymphoid organ responsible for the generation of self-tolerant and competent naive T cells, as well as of self antigen-specific natural regulatory T cells.
Since plasma cell differentiation of self-tolerant B cells is regulated at the early to late pre-plasma cell stage [24], our findings indicate that this tolerance checkpoint is defective in NZB mice.
