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 approximately 10-fold higher titers and was cleared less rapidly from the 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. Analysis with acutely irradiated (950 rads) mice and immunologically reconstituted bone marrow (BM) radiation chimeras indicated that the enhanced virus growth was a function of the radiation-resistant respiratory 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 higher virus-specific serum Ig response skewed towards IgG2a mapped to the 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. Further analysis of double chimeras (B6+129 BM-->B6 recipients) confirmed that the divergent humoral immune response to Sendai virus in B6 and 129 mice is largely determined by the inherent characteristics of the lymphoid cells.
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Department of Pathology, University of Tennessee, Memphis 38163, USA.
Sangster
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Sarawar
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Coleclough
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Doherty
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D000818:Animals; D000917:Antibody Formation; D001853:Bone Marrow / Q000276:immunology / Q000528:radiation effects; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002642:Chick Embryo; D002678:Chimera; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007132:Immunoglobulin Isotypes / Q000032:analysis; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D008168:Lung / Q000821:virology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010222:Parainfluenza Virus 1, Human / Q000276:immunology* / Q000302:isolation & purification; D018184:Paramyxoviridae Infections / Q000276:immunology*; D011024:Pneumonia, Viral / Q000276:immunology*
D016207:Cytokines; D007132:Immunoglobulin Isotypes; D007371:Interferon-gamma