title: Matching antibody class with pathogen type and portal of entry: cognate mechanisms regulate local isotype expression patterns in lymph nodes draining the respiratory tract of mice inoculated with respiratory viruses, according to virus replication competence and site of inoculation.
abstract: Intranasal deposition of Sendai virus (SV) in C57BL/6 mice provokes an Ab-forming cell (AFC) reaction in mediastinal (MLN) and cervical lymph nodes (CLN), which drain the lungs and upper respiratory tract, respectively. While the majority of AFC elicited by infectious SV at both sites produced IgG, the CLN response to SV rendered inactive in replication was restricted almost entirely to IgA, although isotype switching in mediastinal continued to be skewed heavily to IgG. However, in vitro restimulation of the accompanying virus-specific T cell populations from the two sites did not reveal any significant difference in lymphokine output, and isotype expression was not altered substantially in mice lacking IL-4 or IL-6 genes. To dissociate the response to specific Ags from the inflammatory reaction to viral infection, we examined the response to inactivated SV in the face of infection with influenza virus A/HKx31. The magnitude and IgA dominance of the anti-SV AFC population in the CLN were unaffected by a simultaneous, vigorous, IgG-dominated CLN anti-influenza reaction. Evidently, the characteristics of this antiviral response are determined primarily by cognate interactions. Moreover, the IgA bias of the CLN AFC response to inactivated SV was observed only when the virus was delivered intranasally: injection under the epidermis of the cheek, a site that has a lymphatic drainage into the CLN, resulted in an IgG-dominated CLN AFC reaction, lacking IgA. The site of deposition of a vaccine can thus have more influence on the pattern of isotypes induced than the site at which the immune response is initiated.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38101, USA.
authors.forename: M Y
authors.initials: MY
authors.lastname: Sangster
authors.forename: X Y
authors.initials: XY
authors.lastname: Mo
authors.forename: R
authors.initials: R
authors.lastname: Sealy
authors.forename: C
authors.initials: C
authors.lastname: Coleclough
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007132:Immunoglobulin Isotypes / Q000032:analysis*; D015847:Interleukin-4 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010253:Respirovirus Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007132:Immunoglobulin Isotypes; D015850:Interleukin-6; D015847:Interleukin-4