Aberrant presentation of self-lipids by autoimmune B cells depletes peripheral iNKT cells

Aberrant presentation of self-lipids by autoimmune B cells depletes peripheral iNKT cells
Title:
Aberrant presentation of self-lipids by autoimmune B cells depletes peripheral iNKT cells
Other Titles:
Cell Reports
Keywords:
Publication Date:
25 September 2014
Citation:
Tan AH, Chong WP, Ng SW, Basri N, Xu S, Lam KP. Aberrant presentation of self-lipids by autoimmune B cells depletes peripheral iNKT cells. Cell Rep. 2014;9(1):24‐31. doi:10.1016/j.celrep.2014.08.043
Abstract:
Invariant natural killer T (iNKT) cells provide cognate help via CD1d to lipid antigen-presenting B cells for antibody production, but whether B cells reciprocally regulate iNKT cells remains largely unexplored. Here, we found peripheral, but not thymic, iNKT cells to be numerically reduced in autoimmune mice lacking Fas specifically in B cells. The residual iNKT cells were antigenically overstimulated, had altered cytokine production, and manifested enhanced proliferation and apoptosis. B cell-specific ablation of CD1d ameliorated these iNKT defects, suggesting that inappropriate presentation of CD1d-restricted self-lipids by autoimmune B cell-depleted peripheral iNKT cells. CD1d(+) autoimmune B cells have reduced α-galactosidase A expression and, as revealed by lipidomic profiling, altered lipidome with aberrant accumulation of certain self-lipids and reduction of others. These findings unveil a critical link between autoimmunity, B cell lipidome, and the maintenance of peripheral iNKT cells and highlight an essential homeostatic function of B cells beyond antibody production.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
This research is supported by Bioprocessing Technology Institute, A*STAR
Description:
ISSN:
2211-1247
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