Genetic influences on the immune repertoire following tuberculous infection in mice.
Differences in the antibody repertoire between B10 and BALB background strains have been found following intraperitoneal infection of mice with Mycobacterium tuberculosis. Western blot analysis showed that B10 sera reacted with only a few antigenic bands, whereas BALB sera reacted with multiple bands, irrespective of the H-2 (b or k) haplotype. The oligo-banded pattern was a feature of live infection, since immunization with the mycobacterial extract in incomplete Freunds' adjuvant (IFA) produced a multi-banded response in both intact and in previously infected B10 mice. The multibanded BALB phenotype was dominantly expressed in (BALB x B10) F1 hybrids. The extent to which antibody levels to individual antigens varied was influenced by the combined effects of background (non-H-2) and H-2 genes: anti-65,000 molecular weight (MW) and anti-71,000 MW IgG levels were high in BALB but absent or low in B10 mice, irrespective of H-2 haplotypes, anti-19,000 MW levels in B10 mice were strongly H-2 controlled, whilst anti-38,000 MW levels were high in all tested strains. Immunoglobulin G1 (IgG1) subclass antibody and splenic interleukin-4 (IL-4) mRNA levels were distinctly lower in B10 than in BALB mice, but in vitro T-cell proliferative responses to mycobacterial antigens did not differ between the tested strains. It is proposed that the limited extracellular release of mycobacterial antigens required to stimulate B cells and/or differential activation of T-cell subsets may explain the narrow antibody repertoire in B10 strains of mice. This may have relevance to the outcome of infection, as bacterial counts were higher in the BALB strains at 10 weeks post-infection.
Brett
S J
SJ
MRC Tuberculosis and Related Infections Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Ivanyi
J
J
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D000942:Antigens, Bacterial / Q000276:immunology; D015153:Blotting, Western; D006183:H-2 Antigens / Q000235:genetics*; D007074:Immunoglobulin G / Q000032:analysis; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013154:Spleen / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D006183:H-2 Antigens; D007074:Immunoglobulin G; D008222:Lymphokines