DIFFERENTIAL ANTIGEN BURDEN MODULATES THE GAMMA-INTERFERON BUT NOT THE IMMUNOGLOBULIN RESPONSE IN MICE THAT VARY IN SUSCEPTIBILITY TO SENDAI VIRUS PNEUMONIA

Sendai virus, a paramyxovirus which causes murine pneumonia, grew to a pproximately 10-fold higher titers and was cleared less rapidly from t he lungs of 129/J (129) than H-(2b)-compatible C57BL/6J (B6) mice. The more susceptible 129 mice also made higher titers of gamma interferon (IFN-gamma) and immunoglobulin G2a (IgG2a) virus-specific antibody. A nalysis with acutely irradiated (950 rads) mice and immunoIogicalIy re constituted bone marrow (BM) radiation chimeras indicated that the enh anced virus growth was a function of the radiation-resistant respirato ry epithelium. Prolonged exposure to more virus in turn influenced the magnitude of IFN-gamma production, most of which was made by CD4(+) T lymphocytes. Somewhat surprisingly, however, the 129 pattern of a hig her virus-specific serum Ig response skewed towards IgG2a mapped to th e reconstituting BM. Thus, the characteristics of the humoral response are at least partly dissociated from both the antigen load, resulting from viral replication, and the level of IFN-gamma production. Furthe r analysis of double chimeras (B6+129 BM --> B6 recipients) confirmed that the divergent humoral immune response to Sendai virus in B6 and 1 29 mice is largely determined by the inherent characteristics of the l ymphoid cells.