The radioprotective 105/MD-1 complex links TLR2 and TLR4/MD-2 in antibody response to microbial membranes.
Low-affinity IgG3 Abs to microbial membranes are important for primary immune defense against microbes, but little is known about the importance of TLRs in their production. IgG3 levels were extremely low in mice lacking radioprotective 105 (RP105), a B cell surface molecule structurally related to TLRs. RP105(-/-) B cells proliferated poorly in response to not only the TLR4 ligand LPS but also TLR2 ligand lipoproteins, both of which mediate the immunostimulatory activity of microbial membranes. RP105(-/-) mice were severely impaired in hapten-specific Ab production against LPS or lipoproteins. CD138 (syndecan-1)-positive plasma cells were detected after lipid A injection in wild-type spleen but much less in RP105(-/-) spleen. RP105 ligation in vivo induced plasma cell differentiation. RP105 expression was approximately 3-fold higher on marginal zone B cells than on follicular and B1 cells and was down-regulated on germinal center cells. These results demonstrate that a signal via RP105 is uniquely important for regulating TLR-dependent Ab production to microbial membranes.
Nagai
Yoshinori
Y
Divisions of Infectious Genetics and Immunology, Institute of Medical Science, University of Tokyo, Japan.
Kobayashi
Toshihiko
T
Motoi
Yuji
Y
Ishiguro
Kohtaroh
K
Akashi
Sachiko
S
Saitoh
Shin-ichiroh
S
Kusumoto
Yutaka
Y
Kaisho
Tsuneyasu
T
Akira
Shizuo
S
Matsumoto
Mitsuru
M
Takatsu
Kiyoshi
K
Miyake
Kensuke
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000943:Antigens, Differentiation / Q000235:genetics; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D000954:Antigens, Surface / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9
D048868:Adaptor Proteins, Signal Transducing; D000907:Antibodies, Bacterial; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000950:Antigens, Ly; D000954:Antigens, Surface; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D008024:Ligands; D008070:Lipopolysaccharides; C490500:Ly78 protein, mouse; C113553:Ly86 protein, mouse; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9