Signaling via LTbetaR on the lamina propria stromal cells of the gut is required for IgA production

Nat Immunol. 2002 Jun;3(6):576-82. doi: 10.1038/ni795. Epub 2002 May 13.


Peyer's patches (PPs) and/or mesenteric lymph nodes (MLNs) are thought to be essential for immunoglobulin A (IgA) production. We found that the severe IgA deficiency in lymphotoxin-deficient (LT(-/-)) mice could be fully reversed by reconstitution with LT-expressing bone marrow, despite the absence of both LNs and PPs. The number of IgA precursors from LT(-/-) mice was not reduced, and they were able to migrate into the lamina propria (LP) of wild-type mice but not of LTbetaR(-/-) mice. Consistently, lymphoid tissue chemokines and adhesion molecules were reduced within the LP of LTalpha(-/-) and LTbetaR(-/-) mice. IgA deficiency in LTalpha(-/-) mice was reversed by the transplantation of a segment of RAG-1 (recombination-activating gene 1) deficient intestine, which confirmed the dispensability of the MLNs and PPs and the sufficiency of the LT-mediated gut microenvironment for IgA production.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology
  • Cell Adhesion Molecules
  • Chemokines / metabolism
  • Chemotaxis, Leukocyte
  • Female
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Immunoglobulin A / biosynthesis*
  • Immunoglobulins / metabolism
  • Intestines / cytology
  • Intestines / immunology*
  • Intestines / transplantation
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha / genetics
  • Lymphotoxin-alpha / metabolism
  • Mice
  • Mice, Knockout
  • Mucoproteins / metabolism
  • Peyer's Patches / cytology
  • Peyer's Patches / immunology
  • Pregnancy
  • Receptors, Tumor Necrosis Factor / deficiency
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction


  • Cell Adhesion Molecules
  • Chemokines
  • Homeodomain Proteins
  • Immunoglobulin A
  • Immunoglobulins
  • Ltbr protein, mouse
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha
  • Madcam1 protein, mouse
  • Mucoproteins
  • Receptors, Tumor Necrosis Factor
  • RAG-1 protein