Objectives This study focused on understanding the cellular mechanisms involved in the breakdown of tolerance and resulting in the production of autoantibodies in human spleen. Therefore, spleens of patients with immune thrombocytopenia (ITP) were studied as a model of the breakdown of immune tolerance.
Methods 31 spleens from ITP patients and 36 control spleens were analyzed by immunohistochemistry and immunofluorescence, including the detection of antiplatelet reactivity.
Results Two different splenic structures accommodating proliferating B cells within the white pulp, classical germinal centers (GC) and proliferative lymphoid nodules (PLN) were clearly identified. The number of typical GCs was decreased in ITP spleens whereas PLN were prominent and comparable to the number found in normal spleens. Notably, PLN were observed in control and ITP spleens. PLN were characterized by proliferating Ki67+ B cells in close contact with follicular dendritic cells lacking polarization into dark and light zones. As opposed to cells in GC, proliferating B cells in PLN lacked expression of Bcl6. Of note, the density of T cells was reduced in both GC and PLN in ITP in comparison to controls. T follicular helper cells were found within PLN as well as in GC, but the density of Foxp3+ regulatory T cells (Treg) was reduced in both structures in ITP. Strikingly, FDC networks of PLN but not GCs from ITP spleens contained abundant platelet glycoproteinIIb/IIIa autoantigens in IgM containing immune complexes in close proximity to proliferating B cell.
Conclusions This data is consistent with the conclusion that PLN and not GC are the site of the development and maintenance of autoimmunity in ITP, which could be accentuated by the reduced density of Treg in these structures.
Disclosure of Interest None Declared
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