Novel mouse model to study T cell-dependent IgA induction in vivo

J Immunol Methods. 2015 Jun:421:54-60. doi: 10.1016/j.jim.2015.03.001. Epub 2015 Mar 17.

Abstract

Commensal microbiota at the mucosal surfaces controls multiple aspects of body homeostasis. Therefore, regulation of microflora composition by the host is crucial, and one of the mechanisms driving microbiota diversity is the production of large quantities of immunoglobulin A (IgA) at the mucosal surfaces. However, mechanisms of IgA induction in the gut are not completely understood. Here we further characterize a mouse model for studying T cell-dependent IgA production in the gut due to specific genetic ablation of LTβ in RORγt+ cells. Using in utero blockade of the mesenteric lymph node development, we showed that IgA induction in these mice occurs directly in the LP. Furthermore, T cell-dependent IgA inducing mechanism in these mice generates distinct IgA plasma cells producing commensal microflora-binding IgA antibodies. Thus, this model represents a unique in vivo tool for the analysis of T cell-dependent IgA plasma cell generation and their antibody specificity.

Keywords: Immunoglobulin A; Lymphotoxin; Plasma cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Specificity / immunology
  • B-Lymphocytes / immunology
  • Biodiversity
  • Female
  • Immunoglobulin A / biosynthesis*
  • Immunoglobulin A / immunology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Lymphotoxin-beta / genetics
  • Mice
  • Mice, Knockout
  • Microbiota / immunology*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Plasma Cells / immunology
  • Symbiosis
  • T-Lymphocytes / immunology*

Substances

  • Immunoglobulin A
  • Ltb protein, mouse
  • Lymphotoxin-beta
  • Nuclear Receptor Subfamily 1, Group F, Member 3