Role of gut-associated lymphoreticular tissues in antigen-specific intestinal IgA immunity.
This study assessed the roles of the postnatal lymphotoxin-beta receptor (LTbetaR)-mediated signals in the gut-associated lymphoreticular tissues of mice for subsequent regulation of Ag-specific intestinal IgA responses. Blockade of LTbetaR-dependent events by postnatal administration of the fusion protein of LTbetaR and IgG Fc (LTbetaR-Ig) reduced both the size and numbers of Peyer's patches (PP) without influencing the PP microarchitecture. Interestingly, inhibition of LTbetaR-dependent signaling revealed significant reductions in the formation of follicular dendritic cell clusters in mesenteric lymph nodes (MLN). Furthermore, these postnatal signaling events controlled the development of isolated lymphoid follicles (ILF) because treatment with LTbetaR-Ig eliminated the formation of ILF. LTbetaR-Ig-treated mice with altered microarchitecture of MLN and lacking ILF were still able to produce significant Ag-specific mucosal IgA responses after oral immunization; however, the levels were significantly lower than those seen in control mice. These results imply the importance of ILF for Ag-specific intestinal immunity. However, mice treated with both TNFR55-Ig and LTbetaR-Ig in utero, which lack PP and MLN, but retain intact ILF, failed to induce Ag-specific IgA responses after oral immunization. These findings demonstrate that ILF are not essential for induction of intestinal IgA Ab responses to orally administered Ag. Furthermore, the induction of intestinal IgA Ab responses requires the proper maintenance of the MLN microarchitecture, including a follicular dendritic cell network.
Yamamoto
Masafumi
M
Department of Oral Medicine, Nihon University School of Dentistry, Matsudo, Chiba, Japan. fumi@mascat.nihon-u.ac.jp
Kweon
Mi-Na
MN
Rennert
Paul D
PD
Hiroi
Takachika
T
Fujihashi
Kohtaro
K
McGhee
Jerry R
JR
Kiyono
Hiroshi
H
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D053259:Lymphotoxin beta Receptor; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology
D015703:Antigens, CD; D007070:Immunoglobulin A; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I