Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut.
Immunoglobulin A (IgA) is generated in the gut by both T cell-dependent and T cell-independent processes. The sites and the mechanisms for T cell-independent IgA synthesis remain elusive. Here we show that isolated lymphoid follicles (ILFs) were sites where induction of activation-induced cytidine deaminase (AID) and IgA class switching of B cells took place in the absence of T cells. We also show that formation of ILFs was regulated by interactions between lymphoid tissue-inducer cells expressing the nuclear receptor ROR gamma t (ROR gamma t(+)LTi cells) and stromal cells (SCs). Activation of SCs by ROR gamma t(+)LTi cells through lymphotoxin (LT)-beta receptor (LT beta R) and simultaneously by bacteria through TLRs induced recruitment of dendritic cells (DCs) and B cells and formation of ILFs. These findings provide insight into the crosstalk between bacteria, ROR gamma t(+)LTi cells, SCs, DCs, and B cells required for ILF formation and establish a critical role of ILFs in T cell-independent IgA synthesis in gut.
Tsuji
Masayuki
M
Laboratory for Mucosal Immunity, Research Center for Allergy and Immunology, RIKEN Yokohama 1-7-22, Tsurumi, Yokohama, 230-0045, Japan.
Suzuki
Keiichiro
K
Kitamura
Hiroshi
H
Maruya
Mikako
M
Kinoshita
Kazuo
K
Ivanov
Ivaylo I
II
Itoh
Kikuji
K
Littman
Dan R
DR
Fagarasan
Sidonia
S
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D003564:Cytidine Deaminase / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000378:metabolism; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000276:immunology; D017578:Immunoglobulin Class Switching; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D007070:Immunoglobulin A; D053259:Lymphotoxin beta Receptor; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; D003564:Cytidine Deaminase