RT Journal Article SR Electronic T1 B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner JF Annals of the Rheumatic Diseases JO Ann Rheum Dis FD BMJ Publishing Group Ltd and European League Against Rheumatism SP 1537 OP 1544 DO 10.1136/annrheumdis-2021-220435 VO 80 IS 12 A1 Theresa Graalmann A1 Katharina Borst A1 Himanshu Manchanda A1 Lea Vaas A1 Matthias Bruhn A1 Lukas Graalmann A1 Mario Koster A1 Murielle Verboom A1 Michael Hallensleben A1 Carlos Alberto Guzmán A1 Gerd Sutter A1 Reinhold E Schmidt A1 Torsten Witte A1 Ulrich Kalinke YR 2021 UL http://ard.bmj.com/content/80/12/1537.abstract AB Objectives The monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses.Methods CD8+ T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens.Results Rituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8+ T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8+ T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8+ T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I.Conclusions Depending on the stimulus, B cells can modulate CD8+ T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8+ T cell responses.All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article or uploaded as supplementary Information.