title: Mouse CD11bhigh lung dendritic cells have more potent capability to induce IgA than CD103+ lung dendritic cells in vitro.
abstract: Lung dendritic cells (LDCs) are primary antigen-presenting cells that develop IgA-producing plasma cells in the lung through class switch recombination (CSR) in naive B cells. Recently, the major LDC subsets were found to comprise CD103(-)CD11b(high) LDCs (CD11b(high) LDCs) and CD103(+)CD11b(low or negative) LDCs (CD103(+) LDCs), but their abilities to induce IgA production have not been defined. Under T cell-dependent (T-D) and T cell-independent (T-ID) conditions, we compared the abilities of these two LDC populations to induce IgA. CD11b(high) or CD103(+) LDCs obtained from BALB/c mice were cocultured with naive IgD(+) B cells in the presence of LPS, with or without anti-CD40 monoclonal antibody (mAb) (i.e., T-D and T-ID coculture conditions, respectively). Under both T-D and T-ID conditions, CD11b(high) LDCs induced significantly greater amounts of IgA production, together with a significantly higher mRNA expression of activation-induced cytidine deaminase, than did CD103(+) LDCs. However, the protein expression of a proliferation-inducing ligand, B cell-activating factor of the tumor necrosis family, or retinaldehyde dehydrogenase-1 did not differ between the two LDC subsets. CD11b(high) LDCs displayed a significantly greater capacity to secrete IL-6 and IL-10 in response to LPS, with or without anti-CD40 mAb. Moreover, the IgA production induced by CD11b(high) LDCs in T-D coculture was attenuated by neutralizing both IL-6 and IL-10. These findings suggest that, of the two major LDCs, CD11b(high) LDCs more efficiently induce IgA than do CD103(+) LDCs, possibly through their potent capacity to produce IgA-inducing cytokines.
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, Shizuoka, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.forename: Kazuki
authors.initials: K
authors.lastname: Furuhashi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shibata
authors.forename: Dai
authors.initials: D
authors.lastname: Hashimoto
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Enomto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Kingo
authors.initials: K
authors.lastname: Chida
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D015153:Blotting, Western; D039481:CD11b Antigen / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis*; D039001:Integrin alpha Chains / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology*; D051379:Mice; D016133:Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D007070:Immunoglobulin A; D039001:Integrin alpha Chains; C091367:alpha E integrins