Involvement of antibody production quantitative trait loci in the susceptibility to pristane-induced arthritis in the mouse

Abstract

Mice obtained by bidirectional selective breeding for high (HIII) or low (LIII) antibody (Ab) production are resistant or extremely susceptible to pristane-induced arthritis (PIA), respectively. Several quantitative trait loci regulating Ab production (Ab QTL) have been mapped in these lines, which were used to investigate the influence of these Ab QTL in PIA. Parental HIII and LIII mice and their F 1 and F 2 intercrosses were injected twice with pristane, and arthritis was observed for 200 days. In LIII mice PIA was more severe and incidence was 100% at day 105, while F 1 and F 2 mice showed intermediate values. HIII mice were totally resistant. Microsatellite polymorphisms of Ab QTL were analysed and D3Mit100 alleles cosegregated significantly with PIA incidence, severity and onset in F 2 intercross mice, while the other four markers showed suggestive values. Results indicate colocalization of QTL for Ab production and PIA susceptibility. Moreover, the different cytokine and IgG isotype profiles observed in HIII and LIII lines after PIA induction are useful to candidate genes endowed with the regulation of the Ab production and arthritis phenotypes.

Slc11a1 (formerly NRAMP1) gene modulates both acute inflammatory reactions and pristane-induced arthritis in mice

“…In mice, several loci were identified in different models of experimental arthritis. The involvement of acute inflammation 14 and antibody production QTL 27 were demonstrated in PIA development, as well as many other QTL in arthritis models such as those induced by Borrelia burgdorferi, 28 PGIA 29 and CIA. 30 Rheumatoid arthritis is a chronic inflammatory and autoimmune disease characterized by cell accumulation in the sinovium, complement deposition and the production of several proinflammatory cytokines.…”

“…Spleen cells from phosphate-buffered saline (PBS)-or pristane-treated mice were evaluated for IL-6, IL-12, IL-4 and IFNgspecific spot-forming cells. The cytokine ELISPOT assay was performed according to Jensen et al 27 Multiscreen HA 96-well nitrocellulose-based plates (Millipore Corp., Molsheim, France) were coated overnight with capture monoclonal antibodies (mAb) anti-IL-6, IL-12, IL-4 or IFNg (5 mg/ml in PBS). After blocking with RPMI plus 5% fetal calf serum (FCS) for 1 h at room temperature, spleen cells were isolated from PBS-or pristane-treated mice 10, 20, and 75 days after the first injection and incubated (5 Â 10 5 and 10 6 cells/well in duplicate) for 20 h at 371C in a CO 2 incubator.…”

Mycobacterium leprae Hsp65 administration reduces the lifespan of aged high antibody producer mice

“…H III and L III mice, both genders, presented slightly higher production of IgG2a anti-Hsp65 and anti-DNA related to the IgG1 isotype. This balance towards a Th1 response may indicate a natural pro-inflammatory status in these strains which is confirmed by the relative easy way to induce adjuvant arthritis in H III mice [53]. The time-course analyses of immunoglobulin production did not show significant intragroup differences, which might be related to the absence of a strong specific response to these proteins demonstrated by the low antibody titers even 30 days after the protein inoculation and because this is not an immunization process.…”

Trypanosoma cruziInfection in Genetically Selected Mouse Lines: Genetic Linkage with Quantitative Trait Locus Controlling Antibody Response

“…H III and L III lines also show extreme divergence in other phenotypes, such as skin carcinogenesis [31] and pristane induced arthritis—PIA. Our group successfully detected a PIA-susceptibility QTL on chromosome 3 by examining the cosegregation of the most significant Ab QTL markers with arthritis phenotypes [32]. …”