Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut

Immunity. 2008 Aug 15;29(2):261-71. doi: 10.1016/j.immuni.2008.05.014. Epub 2008 Jul 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Communication
  • Cytidine Deaminase / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Gastrointestinal Tract / immunology*
  • Gastrointestinal Tract / metabolism
  • Immunoglobulin A / biosynthesis*
  • Immunoglobulin A / immunology
  • Immunoglobulin Class Switching
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology*
  • Lymphoid Tissue / metabolism
  • Lymphotoxin beta Receptor / immunology
  • Lymphotoxin beta Receptor / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / metabolism
  • Stromal Cells / immunology
  • Stromal Cells / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • Cytokines
  • Immunoglobulin A
  • Lymphotoxin beta Receptor
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • Cytidine Deaminase