Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 209, Issue 10, Pages 1797-1812Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20120332
Keywords
-
Categories
Funding
- National Institutes of Health [PO1 AI022295, RO1 AI052310, RO1 AI052157]
- Viola Vestal Coulter Foundation
Ask authors/readers for more resources
Rare dual-reactive B cells expressing two types of Ig light or heavy chains have been shown to participate in immune responses and differentiate into IgG(+) cells in healthy mice. These cells are generated more often in autoreactive mice, leading us to hypothesize they might be relevant in autoimmunity. Using mice bearing Igk allotypic markers and a wild-type Ig repertoire, we demonstrate that the generation of dual-kappa B cells increases with age and disease progression in autoimmune-prone MRL and MRL/lpr mice. These dual-reactive cells express markers of activation and are more frequently autoreactive than single-reactive B cells. Moreover, dual-kappa B cells represent up to half of plasmablasts and memory B cells in autoimmune mice, whereas they remain infrequent in healthy mice. Differentiation of dual-kappa B cells into plasmablasts is driven by MRL genes, whereas the maintenance of IgG(+) cells is partly dependent on Fas inactivation. Furthermore, dual-kappa B cells that differentiate into plasmablasts retain the capacity to secrete autoantibodies. Overall, our study indicates that dual-reactive B cells significantly contribute to the plasmablast and memory B cell populations of autoimmune-prone mice suggesting a role in autoimmunity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available