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

Intranasal deposition of Sendai virus (SV) in C57BL/6 mice provokes an Ab-forming cell (AFC) reaction in mediastinal (MLN) and cervical lymp h nodes (CLN), which drain the lungs and upper respiratory tract, resp ectively. While the majority of AFC elicited by infectious SV at both sites produced IgG, the CLN response to SV rendered inactive in replic ation was restricted almost entirely to IgA, although isotype switchin g in mediastinal continued to be skewed heavily to IgG. However, in vi tro restimulation of the accompanying virus-specific T cell population s from the two sites did not reveal any significant difference in lymp hokine output, and isotype expression was not altered substantially in mice lacking IL-4 or IL-6 genes. To dissociate the response to specif ic 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 pop ulation in the CLN were unaffected by a simultaneous, vigorous. IgG-do minated CLN anti-influenza reaction. Evidently, the characteristics of this antiviral response are determined primarily by cognate interacti ons. 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 drainag e 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.