@article{Krystalyn E. Hudson_Jeanne E. Hendrickson_Chantel M. Cadwell_Neal N. Iwakoshi_James C. Zimring_2012, place={Pavia, Italy}, title={Partial tolerance of autoreactive B and T cells to erythrocyte-specific self-antigens in mice}, volume={97}, url={https://haematologica.org/article/view/6498}, DOI={10.3324/haematol.2012.065144}, abstractNote={<strong>Background</strong> Breakdown of humoral tolerance to RBC antigens may lead to autoimmune hemolytic anemia, a severe and sometimes fatal disease. The underlying mechanisms behind the breakdown of humoral tolerance to RBC antigens are poorly understood.<strong>Design and Methods</strong> In order to study the pathogenesis of autoimmune hemolytic anemia, we developed a murine model with RBC-specific expression of a model antigen carrying epitopes from hen egg lysozyme and ovalbumin.<strong>Results</strong> Humoral tolerance was observed; this was not broken even by strong immunogenic stimulation (lysozyme or ovalbumin with adjuvant). Autoreactive CD4<sup>+</sup> T cells were detected by tetramer enrichment assays, but failed to activate or expand despite repeat stimulation, indicating a nonresponsive population rather than deletion. Adoptive transfer of autoreactive CD4<sup>+</sup> T cells (OT-II mice) led to autoantibody (anti-lysozyme) production by B cells in multiple anatomic compartments, including the bone marrow.<strong>Conclusions</strong&gt; These data demonstrate that B cells autoreactive to RBC antigens survive in healthy mice with normal immune systems. Furthermore, autoreactive B cells are not centrally tolerized and are receptive to T-cell help. As the autoreactive T cells are present but non-responsive, these data indicate that factors that reverse T-cell non-responsiveness may be central to the pathogenesis of autoimmune hemolytic anemia.}, number={12}, journal={Haematologica}, author={Krystalyn E. Hudson and Jeanne E. Hendrickson and Chantel M. Cadwell and Neal N. Iwakoshi and James C. Zimring}, year={2012}, month={Nov.}, pages={1836-1844} }