T-H cells primed during influenza virus infection provide help for qualitatively distinct antibody responses to subsequent immunization

The quality of the primary Ab-forming cell (AFC) response in cervical lymph nodes and mediastinal lymph nodes of mice to intranasal influenza virus wa s strongly influenced by viral replicative capacity. IgA secretors were pro minent in the early AFC response to infectious virus in mediastinal lymph n odes, while IgG expression was more frequent among isotypically switched AF C in cervical lymph nodes of the same mice; this pattern was reversed in th e response to inactivated virus. Influenza viruses A/PuertoRico/8/34 (A/PR8 ) and A/X-31 share six of eight genome segments, differing only in hemagglu tinin (H1 in A/PR8, H3 in A/X-31) and neuraminidase (N1 in A/PR8, N2 in A/X -31) genes. These-viruses therefore elicit extensively cross-reactive Tn po pulations, though their glycoproteins are serologically unrelated. Mice rec overed from an A/X-31 infection thus mount a primary B cell response agains t A/PR8 glycoproteins, when challenged with the latter virus, though this r esponse can call upon memory T-H cells. To assess the impact of memory T-H populations on a primary Ab response, we compared the AFC response to inact ivated A/PR8 in naive mice and mice that had cleared an A/X-31 infection. A /X-31 immune mice mounted a more vigorous AFC response against A/PR8 H1 and N1 glycoproteins than naive animals, when, immunized intranasally with ina ctivated A/PR8 However the distribution of isotypes among H1/N1-specific AF C in lymph nodes of A/X-31-primed mice resembled that of naive mice, Eviden tly, in this functional context, memory T-H cells retained the ability to h elp Ab responses different in quality from that generated during their prim ary reaction.