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Haematologica. 2012 Dec;97(12):1836-44. doi: 10.3324/haematol.2012.065144. Epub 2012 Jun 24.

Partial tolerance of autoreactive B and T cells to erythrocyte-specific self-antigens in mice.

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  • 1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Abstract

BACKGROUND:

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.

DESIGN AND METHODS:

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.

RESULTS:

Humoral tolerance was observed; this was not broken even by strong immunogenic stimulation (lysozyme or ovalbumin with adjuvant). Autoreactive CD4(+) 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(+) T cells (OT-II mice) led to autoantibody (anti-lysozyme) production by B cells in multiple anatomic compartments, including the bone marrow.

CONCLUSIONS:

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.

PMID:
22733018
[PubMed - indexed for MEDLINE]
PMCID:
PMC3590090
Free PMC Article

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