title: Gut-associated lymphoid tissue contains the molecular machinery to support T-cell-dependent and T-cell-independent class switch recombination.
abstract: A PRoliferation-Inducing Ligand (APRIL) is a secreted cytokine member of the tumor necrosis factor family. It is a B-cell survival factor that also induces class switch recombination (CSR) toward immunoglobulin A (IgA), independent of T cells. It is therefore an important contributor to the maintenance of the mucosal immunological barrier, which has been linked to a putative extrafollicular inductive phase of the IgA response in lamina propria. By immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) on microdissected tissue from normal human gut, we observed APRIL expression, together with TACI (transmembrane activator and CAML interactor) and BCMA (B-cell maturation antigen), in gut-associated lymphoid tissue (GALT), lamina propria, and in the epithelium of stomach, small and large intestine, and rectum. However, no activation-induced cytidine deaminase (AID) expression (an absolute requirement for class switching) was detected in lamina propria by IHC or qRT-PCR. APRIL and its receptors were only observed alongside AID in GALT, showing that GALT contains the apparatus to support both T-independent and T-dependent routes to IgA CSR.
authors.affiliation: Peter Gorer Department of Immunobiology, King's College London, London, UK.
authors.forename: F
authors.initials: F
authors.lastname: Barone
authors.forename: P
authors.initials: P
authors.lastname: Patel
authors.forename: J D
authors.initials: JD
authors.lastname: Sanderson
authors.forename: J
authors.initials: J
authors.lastname: Spencer
mesh_terms: D053301:B-Cell Maturation Antigen / Q000096:biosynthesis / Q000276:immunology; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000276:immunology; D005753:Gastric Mucosa / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism; D042282:Microdissection; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D053303:Transmembrane Activator and CAML Interactor Protein / Q000096:biosynthesis / Q000276:immunology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000096:biosynthesis / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D053301:B-Cell Maturation Antigen; D007070:Immunoglobulin A; C108467:TNFRSF13B protein, human; C086966:TNFRSF17 protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase