title: The presence of MOMA-2+ macrophages in the outer B cell zone and protection of the splenic micro-architecture from LPS-induced destruction depend on secreted IgM.
abstract: The role secretory IgM has in protecting splenic tissue from LPS-induced damage was assessed in mice incapable of secreting IgM but able to express surface IgM and IgD. Within seconds after LPS challenge, 99% of the (131)I-labeled LPS was found in the liver and the spleen of both sIgM-deficient and wild-type mice. In the spleen FITC-labeled LPS was found on the surface of 2F8(+) scavenger receptor macrophages localized in the outer marginal zone, while none of the labeled LPS could be detected on marginal zone ER-TR9(+) and MOMA-1(+) macrophages. An additional population of macrophages, MOMA-2(+), were capable of producing C3 locally in the T and B cell zone after LPS challenge. Local C3 production was regulated, as no C3 was found in splenic tissue of unchallenged mice. Interestingly, in the absence of circulating and locally produced secretory IgM, MOMA-2(+) macrophages of the T and B cell zone failed to establish an additional ring of C3-producing macrophages in the outer B cell zone close to the marginal zone upon LPS challenge. The consequence was a massive destruction of the microarchitecture of the spleen where marginal zones disorganized, lymphoid follicles and T cell zones disrupted and follicular DC (FDC) networks disappeared.
authors: Department of Transfusion Medicine, Medical University of Vienna, Vienna, Austria. michael.b.fischer@meduniwien.ac.at
authors: Michael B
authors: MB
authors: Fischer
authors: Beate
authors: B
authors: Rüger
authors: Christine
authors: C
authors: Vaculik
authors: Alexander
authors: A
authors: Becherer
authors: Wolfgang
authors: W
authors: Wadsak
authors: Genya
authors: G
authors: Yanagida
authors: Udo M
authors: UM
authors: Losert
authors: Jianzhu
authors: J
authors: Chen
authors: Michael C
authors: MC
authors: Carroll
authors: Martha M
authors: MM
authors: Eibl
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003176:Complement C3 / Q000502:physiology; D007075:Immunoglobulin M / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology* / Q000633:toxicity; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D003176:Complement C3; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; C036763:monocyte-macrophage differentiation antigen; C033027:secretory IgM