Generation of circulating autoreactive pre-plasma cells fueled by naive B cells in celiac disease

Cell Rep. 2024 Apr 23;43(4):114045. doi: 10.1016/j.celrep.2024.114045. Epub 2024 Apr 4.


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.

Keywords: B cells; CD27; CP: Immunology; IgA; antibodies; autoimmunity; celiac disease; mucosal immunology; plasma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • B-Lymphocytes* / immunology
  • B-Lymphocytes* / metabolism
  • Celiac Disease* / immunology
  • Celiac Disease* / pathology
  • Female
  • GTP-Binding Proteins* / immunology
  • GTP-Binding Proteins* / metabolism
  • Glutens / immunology
  • Humans
  • Immunoglobulin A* / blood
  • Immunoglobulin A* / immunology
  • Immunoglobulin A* / metabolism
  • Male
  • Middle Aged
  • Plasma Cells* / immunology
  • Plasma Cells* / metabolism
  • Protein Glutamine gamma Glutamyltransferase 2*
  • Transglutaminases* / immunology
  • Transglutaminases* / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism


  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • Immunoglobulin A
  • GTP-Binding Proteins
  • Autoantibodies
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Glutens