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The 1E03 immunoglobulin knock-in mouse produces B cells reactive to deamidated gluten peptides (DGP). The transfer of DGP-specific B cells and immunization with a DGP-cholera toxin conjugate led to the formation of DGP-reactive small-intestinal lamina propria plasma cells and serum antibodies. This model enables studies of plasma cells associated with celiac disease.<\/p>\n
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Celiac disease is an autoimmune enteropathy caused by aberrant immune responses to dietary gluten peptides. Plasma cells (PCs) reactive with deamidated gluten peptides (DGP) or transglutaminase 2 are abundant in celiac disease gut lesions, yet their role in disease pathogenesis remains unclear. Here, we present a mouse model that allows for exploring the role of DGP-specific IgA PCs. This model employs a novel immunoglobulin knock-in (Ig KI) mouse expressing a celiac-patient-derived anti-DGP B-cell receptor (BCR) that recognizes an immunodominant DGP epitope. In these mice, \u223c80% of splenic B cells express the transgenic BCR. In co-culture experiments with transgenic DGP-specific B cells and transgenic gluten-specific CD4+<\/sup> T cells, stimulation with DGP led to T-cell and B-cell proliferation. Mice carrying the celiac disease-associated human leukocyte antigen (HLA) allotype HLA-DQ2.5 developed DGP-specific small intestinal IgA PCs upon adoptive transfer of HLA-DQ2.5-expressing DGP-specific B cells and oral immunizations with DGP and cholera toxin (CT). However, covalent conjugation of DGP to CT was required for effective anti-DGP gut immunity. This novel mouse model provides an important tool for studying the role of PCs beyond antibody production in celiac disease.<\/p>","protected":false},"excerpt":{"rendered":" The 1E03 immunoglobulin knock-in mouse produces B cells reactive to deamidated gluten peptides (DGP). The transfer of DGP-specific B cells and immunization with a DGP-cholera toxin conjugate led to the formation of DGP-reactive small-intestinal lamina propria plasma cells and serum antibodies. This model enables studies of plasma cells associated with celiac disease. ABSTRACT Celiac disease … Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[112,42],"tags":[],"class_list":["post-27691","post","type-post","status-publish","format-standard","hentry","category-european-journal-of-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/27691","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=27691"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/27691\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=27691"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=27691"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=27691"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}