Collaboration between B cells and T cells in celiac disease

Collaboration between B cells and T cells in celiac disease

B cells are now recognized as key players in autoimmune diseases traditionally thought to be T cell-mediated. B cells can present antigens, which stimulate immune responses, to T cells in autoimmune diseases, but the role of B cells as antigen-presenting cells is not well understood.

Researchers examined the autoantibody response against the enzyme transglutaminase 2 (TG2) in celiac disease, an autoimmune disorder characterized by abnormal sensitivity to gluten proteins found in wheat, rye, and barley.

B cells that specifically bind epitopes in the N-terminal domain of TG2 more efficiently took up TG2-gluten complexes for presentation to gluten-specific T cells, compared with B cells that specifically recognize C-terminal TG2 epitopes.

Moreover, TG2-specific antibodies from blood samples from patients with different degrees of intestinal inflammation showed a preference for binding to N-terminal versus C-terminal TG2 epitopes. This N-terminal bias was especially pronounced in some children with recently developed celiac disease, compared with adults with established, untreated disease.

According to the authors, the results suggest that the preferential targeting of certain N-terminal TG2 epitopes is prominent shortly after disease onset, and that B cells with this form of specificity may be the main antigen-presenting cells for pathogenic gluten-specific T cells.