title: Oral-nasopharyngeal dendritic cells mediate T cell-independent IgA class switching on B-1 B cells.
abstract: Native cholera toxin (nCT) as a nasal adjuvant was shown to elicit increased levels of T-independent S-IgA antibody (Ab) responses through IL-5- IL-5 receptor interactions between CD4+ T cells and IgA+ B-1 B cells in murine submandibular glands (SMGs) and nasal passages (NPs). Here, we further investigate whether oral-nasopharyngeal dendritic cells (DCs) play a central role in the induction of B-1 B cell IgA class switch recombination (CSR) for the enhancement of T cell-independent (TI) mucosal S-IgA Ab responses. High expression levels of activation-induced cytidine deaminase, Iα-Cμ circulation transcripts and Iμ-Cα transcripts were seen on B-1 B cells purified from SMGs and NPs of both TCRβ⁻/⁻ mice and wild-type mice given nasal trinitrophenyl (TNP)-LPS plus nCT, than in the same tissues of mice given nCT or TNP-LPS alone. Further, DCs from SMGs, NPs and NALT of mice given nasal TNP-LPS plus nCT expressed significantly higher levels of a proliferation-inducing ligand (APRIL) than those in mice given TNP-LPS or nCT alone, whereas the B-1 B cells in SMGs and NPs showed elevated levels of transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI) expression. Interestingly, high frequencies of IgA+ B-1 B cells were induced when peritoneal IgA⁻ IgM+ B cells were stimulated with mucosal DCs from mice given nasal TNP-LPS plus nCT. Taken together, these findings show that nasal nCT plays a key role in the enhancement of mucosal DC-mediated TI IgA CSR by B-1 B cells through their interactions with APRIL and TACI.
authors: Department of Preventive Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Kosuke
authors: K
authors: Kataoka
authors: Keiko
authors: K
authors: Fujihashi
authors: Yutaka
authors: Y
authors: Terao
authors: Rebekah S
authors: RS
authors: Gilbert
authors: Shinichi
authors: S
authors: Sekine
authors: Ryoki
authors: R
authors: Kobayashi
authors: Yoshiko
authors: Y
authors: Fukuyama
authors: Shigetada
authors: S
authors: Kawabata
authors: Kohtaro
authors: K
authors: Fujihashi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D053265:B-Cell Activation Factor Receptor / Q000235:genetics; D053301:B-Cell Maturation Antigen / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007070:Immunoglobulin A / Q000737:chemistry / Q000276:immunology*; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D009061:Mouth Mucosa / Q000276:immunology*; D009305:Nasopharynx / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013363:Submandibular Gland / Q000276:immunology; D013601:T-Lymphocytes; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; C490314:Caml protein, mouse; D007070:Immunoglobulin A; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; C048761:trinitrophenyl-lipopolysaccharide; D002772:Cholera Toxin