AUTHOR=Pollmann Robert , Walter Elias , Schmidt Thomas , Waschke Jens , Hertl Michael , Möbs Christian , Eming Rüdiger 

TITLE=Identification of Autoreactive B Cell Subpopulations in Peripheral Blood of Autoimmune Patients With Pemphigus Vulgaris

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01375

DOI=10.3389/fimmu.2019.01375

ISSN=1664-3224

ABSTRACT=<p>Pemphigus vulgaris (PV) is a rare blistering disease caused by IgG autoantibodies against the epidermal adhesion molecules desmoglein (Dsg)3 and Dsg1 providing a well-characterized paradigm of an antibody-mediated organ-specific autoimmune disease. In PV patients who have achieved clinical remission after B cell-depleting therapy, relapses often coincide with a reoccurrence of B cells and Dsg-specific autoantibodies. Here, we analyzed Dsg3-specific B cell subpopulations (i.e., total CD19<sup>+</sup> B cells, CD19<sup>+</sup>CD27<sup>−</sup>B cells, CD19<sup>+</sup>CD27<sup>+</sup> memory B cells, and CD19<sup>+</sup>CD27<sup>hi</sup>CD38<sup>hi</sup> plasmablasts) in peripheral blood of both PV patients (<italic>n</italic> = 14) at different stages of disease and healthy individuals (<italic>n</italic> = 14) by flow cytometry using fluorescently labeled recombinant human Dsg3 protein. Applying this approach, Dsg3-specific B cells could be detected at low frequencies (0.11–0.53% of CD19<sup>+</sup> B cells) and numbers of Dsg3-specific memory B cells were significantly increased in PV patients in clinical remission receiving minimal immunosuppressive therapy. Finally, we confirmed <italic>in vitro</italic> that Dsg3-reactive memory B cells were able to produce anti-Dsg3 IgG autoantibodies upon <italic>ex vivo</italic> activation. Thus, monitoring of Dsg3-specific B cells in PV is of particular interest to further characterize the immunopathogenesis of PV.</p>