| First Author | Aas-Hanssen K | Year | 2014 |
| Journal | J Immunol | Volume | 193 |
| Issue | 6 | Pages | 2691-8 |
| PubMed ID | 25127856 | Mgi Jnum | J:357983 |
| Mgi Id | MGI:6837722 | Doi | 10.4049/jimmunol.1400640 |
| Citation | Aas-Hanssen K, et al. (2014) Idiotype-specific Th cells support oligoclonal expansion of anti-dsDNA B cells in mice with lupus. J Immunol 193(6):2691-8 |
| abstractText | Systemic lupus erythematosus (SLE) is marked by a Th cell-dependent B cell hyperresponsiveness, with frequent germinal center reactions and hypergammaglobulinemia. The specificity of Th cells in lupus remains unclear, but B cell Ids have been suggested. A hallmark is the presence of anti-dsDNA, mutated IgG autoantibodies with a preponderance of arginines in CDR3 of the Ig variable H chain (IgVH). B cells can present V region-derived Id peptides on their MHC class II molecules to Id-specific Th cells. We show that Id-specific Th cells support the proliferation of anti-dsDNA Id(+) B cells in mice suffering from systemic autoimmune disease with SLE-like features. Mice developed marked clonal expansions of B cells; half of the IgVH sequences were clonally related. Anti-dsDNA B cells made up 40% of B cells in end-stage disease. The B cells expressed mutated IgVH with multiple arginines in CDR3. Hence, Id-driven T cell-B cell collaboration supported the production of classical anti-dsDNA Abs, recapitulating the characteristics of such Abs in SLE. The results support the concept that Id-specific Th cells may trigger the development of SLE and suggest that manipulation of the Id-specific T cell repertoire could play a role in treatment. |
