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

Abstract

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.

• Authors: Hyung-Sik Kang, Robert K Chin, Yang Wang, Ping Yu, Jun Wang, Kenneth A Newell, Yang-Xin Fu
• Journal: Nature immunology (Nat Immunol) Vol. 3 Issue 6 Pg. 576-82 (Jun 2002) ISSN: 1529-2908 [Print] United States
• PMID: 12006975 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 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

Topics

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