title: Distribution and phenotype of rotavirus-specific B cells induced during the antigen-driven primary response to 2/6 virus-like particles administered by the intrarectal and the intranasal routes.
abstract: Selection of mucosal sites is an important step in mucosal vaccine development. The intrarectal (IR) route represents an alternative to the oral route of immunization; nevertheless, immune responses induced by this route are not well defined. Here, we studied the early primary B cell response (induction, homing, and phenotype) induced by IR immunization with rotavirus (RV)-2/6 virus-like particles (VLP). Using flow cytometry, we traced RV-specific B cells in different lymphoid tissues and analyzed the expression of alpha4beta7 and CCR9, which are important receptors for homing to the gut, as well as CD5, a marker expressed by B1-a cells, which are a major source of natural antibodies. We observed a massive, specific B cell response in rectal follicles, lumbar, and mesenteric lymph nodes but not in Peyer's patches or cervical lymph nodes. A minority of cells expressed alpha4beta7, suggesting a probable lack of migration to the gut, whereas CCR9 and CD5 were expressed by 30-50% and 30-75% of specific B cells, respectively. Then, we compared the intranasal route of immunization and observed similar B cell frequency and phenotype but in respiratory lymphoid tissues. These results confirm the high compartmentalization of B cell responses within the mucosal system. They show that CCR9 expression, conversely to alpha4beta7, is not restricted to B cells induced in the gut. Finally, an important part of the RV-specific B cell response induced at the mucosal level during the primary response to VLP is most likely a result of B1-a cells.
authors.affiliation: Laboratoire des Interactions Muqueuses-Agents transmissibles LIMA, UPR562, UFRs Médecine et Pharmacie, IFR 100 Santé-STIC, Université de Bourgogne, Dijon, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Di Martino
authors.forename: Christelle
authors.initials: C
authors.lastname: Basset
authors.forename: Agathe
authors.initials: A
authors.lastname: Ogier
authors.forename: Annie
authors.initials: A
authors.lastname: Charpilienne
authors.forename: Didier
authors.initials: D
authors.lastname: Poncet
authors.forename: Evelyne
authors.initials: E
authors.lastname: Kohli
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D005260:Female; D018928:Immunity, Mucosal / Q000187:drug effects; D007114:Immunization; D007422:Intestines / Q000276:immunology; D008161:Lumbosacral Region; D008198:Lymph Nodes / Q000276:immunology; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches; D010641:Phenotype; D054388:Receptors, CCR / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D012401:Rotavirus / Q000276:immunology*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; C119309:CC chemokine receptor 9; D018956:CD5 Antigens; D054388:Receptors, CCR; D016201:Receptors, Lymphocyte Homing; D022243:Rotavirus Vaccines