We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Separate checkpoints regulate splenic plasma cell accumulation and IgG autoantibody production in Lyn-deficient mice.
- Authors
Gutierrez, Toni; Halcomb, Kristina E.; Coughran, Alanna J.; Li, Quan-Zhen; Satterthwaite, Anne B.
- Abstract
Accumulation of plasma cells and autoantibodies against nuclear antigens characterize both human and murine lupus. Understanding how these processes are controlled may reveal novel therapeutic targets for this disease. Mice deficient in Lyn, a negative regulator of B and myeloid cell activity, develop lupus-like autoimmune disease. Here, we show that lyn mice exhibit increased splenic plasmablasts and plasma cells and produce IgM against a wide range of self-antigens. Both events require Btk, a target of Lyn-dependent inhibitory pathways. A Btk-dependent increase in the expression of the plasma cell survival factor IL-6 by lyn splenic myeloid cells was also observed. Surprisingly, IL-6 was not required for plasma cell accumulation or polyclonal IgM autoreactivity in lyn mice. IL-6 was, however, necessary for the production of IgG autoantibodies, which we show are focused towards a limited set of nucleic acid-containing and glomerular autoantigens in lyn mice. A similar uncoupling of plasma cell accumulation from IgG autoantibodies was seen in lyn mice. Plasma cell accumulation and polyclonal IgM autoreactivity are therefore controlled separately from, and are insufficient for, the production of IgG against lupus-associated autoantigens. Regulators of either of these two checkpoints may be attractive therapeutic targets for lupus.
- Publication
European Journal of Immunology, 2010, Vol 40, Issue 7, p1897
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200940043