title: Regulation of the development of the hepatic B cell compartment during Schistosoma mansoni infection.
abstract: During infection with the helminth parasite Schistosoma mansoni, Ab regulates hepatic inflammation, and local production of Ig in the liver appears to play a role in this process. Exploring the development of the B cell response during infection, we found that parasite-specific IgG1-secreting plasma cells appeared first in the hepatic and mesenteric lymph nodes (LNs) and then at later times in the spleen, liver, and bone marrow. The LN B cell population peaked between weeks 10 and 12 of infection, and then contracted at a time that coincided with the expansion of the hepatic IgG1(+) B cell compartment, suggesting that B cells migrate from LNs to liver. CXCL9 and -16 expression in the liver increased during the time frame of B cell recruitment. Expression of the CXCL16 receptor CXCR6 was increased on B cells within the hepatic LNs, but not the mesenteric LNs. CXCR3, the receptor for CXCL9, was broadly expressed on IgG1(+) B cells in LNs and liver during infection. Increased hepatic expression of CXCL9 and -16 failed to occur if the IL-10R was blocked in vivo, an intervention associated with decreased liver B cell infiltration and the development of severe disease. Hepatic LN IgG1(+) cells migrated toward CXCL9 and -16 in vitro and to the liver in a pertussis toxin-sensitive fashion. Our data suggest that the coordinated expression of CXCL9 and -16 in the liver and of CXCR6 and CXCR3 on responding B cells within the hepatic LNs underpins establishment of the hepatic B cell infiltrate during chronic schistosomiasis.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Keke C
authors.initials: KC
authors.lastname: Fairfax
authors.forename: Bart
authors.initials: B
authors.lastname: Everts
authors.forename: Amber M
authors.initials: AM
authors.lastname: Smith
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Pearce
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000096:biosynthesis; D054370:Chemokine CXCL9 / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D037342:Pertussis Toxin; D054387:Receptors, CXCR / Q000096:biosynthesis; D054367:Receptors, CXCR3 / Q000096:biosynthesis; D000075744:Receptors, CXCR6; D053701:Receptors, Interleukin-10 / Q000096:biosynthesis; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D054370:Chemokine CXCL9; C498926:Cxcl16 protein, mouse; C485969:Cxcl9 protein, mouse; C515188:Cxcr3 protein, mouse; C482906:Cxcr6 protein, mouse; D007074:Immunoglobulin G; D054387:Receptors, CXCR; D054367:Receptors, CXCR3; D000075744:Receptors, CXCR6; D053701:Receptors, Interleukin-10; D037342:Pertussis Toxin
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