IGG ISOTYPE DISTRIBUTION OF LOCAL AND SYSTEMIC IMMUNE-RESPONSES INDUCED BY INFLUENZA-VIRUS INFECTION

The IgG isotype profile of the influenza virus-specific immune respons e was studied by quantitation of serum antibody (Ab) levels in correla tion with the enumeration of antibody-secreting cells (ASC) detected i n the lung, spleen, mediastinal lymph nodes (MLN), Peyer's patches and bone marrow (BM). Distincst isotypic patterns for serum Ab and Ab pro duced by cells present at or close to the site of infection were found after primary or repeated infections. An elevated number of IgM ASC w as found after primary challenge in the spleen, lung and MLN. In contr ast, the site of IgA and IgG production is restricted to the lung and lymph nodes draining the site of infection. In these organs IgA, IgG2a and IgG1 ASC are found as a result of primary virus infection while v iral challenge induces mostly activation of IgA-producing cells and se cretion of IgA to the lung lavage. In contrast, the majority (80-90%) of Ab detected in the serum belong to the IgG2a subclass and their ser um level is maintained at a high level during the whole period of the response. The relative level of virus-specific serum IgG2a in correlat ion with the production of IgG2a Ab found predominantly in MLN and lun g is highly dependent on the viral dose used for priming or challenge. As IgG2a ASC can be detected at relatively low numbers in the spleen and BM these results suggest that the production of the dominant IgG2a isotype of serum Ab occurs close to the viral challenge site. These d ata, however, point to distinct isotypic regulation in systemic versus local virus-specific Ab responses.