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Age-Associated Increase of CD5 + B Cells in the Liver of Autoimmune (NZB × NZW) F 1 Mice

1993; Wiley; Volume: 37; Issue: 3 Linguagem: Inglês

10.1111/j.1348-0421.1993.tb03203.x

1348-0421

Toshiaki Ohteki, Toru Abo, Akinori Kusumi, Takeshi Sasaki, S Shibata, Shuhji Seki, Katsuo Kumagai,

Immune Cell Function and Interaction

Abstract The liver has been demonstrated to be a major site for extrathymic differentiation of T cells. In this study, an identification of CD5 + B cells, which are responsible for the onset of autoimmune disease by virtue of autoantibody production, was performed in autoimmune (NZB × NZW) F 1 mice. An age‐associated increase of CD5 + B cells was demonstrated in the liver of these mice. Although CD5 + B cells (i.e., CD5 + IgM + and CD5 + B220 + ) constituted a minor population of hepatic mononuclear cells (MNC) (<5%) when mice were young (8 weeks), a large population of CD5 + B cells (10 to 30% of whole MNC) was identified in the liver of mice aged 25 to 30 weeks after the onset of disease. Such age‐dependent increase of CD5 + B cells was not observed in any other strains including NZB, NZW, C3H/He and BALB/c mice. The phenotype of hepatic CD5 + B cells was the same as that of CD5 + B cells in the peritoneal cavity and spleen, showing dull‐CD5, bright‐IgM and dull‐B220. High levels of CD5 + B cells were observed in the peritoneal cavity and liver, but not in the spleen nor in any other lymphoid organs in mice aged 30 weeks. Radioimmunoassay of autoantibodies in the 5‐day culture supernatants demonstrated that hepatic MNC were unable to produce any amounts of IgM‐ and IgG‐autoantibodies against double‐stranded DNA and single‐stranded DNA, despite the increased proportion of CD5 + B cells. On the other hand, peritoneal exudate cells produced only IgM‐, but not IgG‐, autoantibodies, whereas splenic cells were able to produce both IgM‐ and IgG‐autoantibodies. These results suggest that the liver might support the generation of the most primitive CD5 + B cells in these mice and that such generation increases as a function of age, probably resulting in the onset of autoimmune disease.