Signaling via LTbetaR on the lamina propria stromal cells of the gut is required for IgA production.
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.
Kang
Hyung-Sik
HS
Department of Pathology and Committee on Immunology, The University of Chicago, 5841 S. Maryland, Chicago, IL 60637, USA.
Chin
Robert K
RK
Wang
Yang
Y
Yu
Ping
P
Wang
Jun
J
Newell
Kenneth A
KA
Fu
Yang-Xin
YX
D019264:Adoptive Transfer; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D015815:Cell Adhesion Molecules; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007136:Immunoglobulins / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009088:Mucoproteins / Q000378:metabolism; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology; D011247:Pregnancy; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; D018925:Chemokines; D018398:Homeodomain Proteins; D007070:Immunoglobulin A; D007136:Immunoglobulins; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D018124:Receptors, Tumor Necrosis Factor; C064658:RAG-1 protein