Generation of circulating autoreactive pre-plasma cells fueled by naive B cells in celiac disease
Ida Lindeman,
Lene S. Høydahl,
Asbjørn Christophersen,
Louise F. Risnes,
Jørgen Jahnsen,
Knut E.A. Lundin,
Ludvig M. Sollid,
Rasmus Iversen
Affiliations
Ida Lindeman
Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital – Rikshospitalet, Oslo, Norway
Lene S. Høydahl
Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital – Rikshospitalet, Oslo, Norway
Asbjørn Christophersen
Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital – Rikshospitalet, Oslo, Norway
Louise F. Risnes
Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital – Rikshospitalet, Oslo, Norway
Jørgen Jahnsen
Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
Knut E.A. Lundin
Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterology, Oslo University Hospital – Rikshospitalet, Oslo, Norway
Ludvig M. Sollid
Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital – Rikshospitalet, Oslo, Norway
Rasmus Iversen
Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital – Rikshospitalet, Oslo, Norway; Corresponding author
Summary: Autoantibodies against the enzyme transglutaminase 2 (TG2) are characteristic of celiac disease (CeD), and TG2-specific immunoglobulin (Ig) A plasma cells are abundant in gut biopsies of patients. Here, we describe the corresponding population of autoreactive B cells in blood. Circulating TG2-specific IgA cells are present in untreated patients on a gluten-containing diet but not in controls. They are clonally related to TG2-specific small intestinal plasma cells, and they express gut-homing molecules, indicating that they are plasma cell precursors. Unlike other IgA-switched cells, the TG2-specific cells are negative for CD27, placing them in the double-negative (IgD−CD27−) category. They have a plasmablast or activated memory B cell phenotype, and they harbor fewer variable region mutations than other IgA cells. Based on their similarity to naive B cells, we propose that autoreactive IgA cells in CeD are generated mainly through chronic recruitment of naive B cells via an extrafollicular response involving gluten-specific CD4+ T cells.
