B cell depletion reduces the development of atherosclerosis in mice
(2010) The Journal of Experimental Medicine — Vol. 207, n° 8, p. 1579-1587 (2010)
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- B cell depletion significantly reduces the burden of several immune-mediated diseases. However, B cell activation has been until now associated with a protection against atherosclerosis, suggesting that B cell-depleting therapies would enhance cardiovascular risk. We unexpectedly show that mature B cell depletion using a CD20-specific monoclonal antibody induces a significant reduction of atherosclerosis in various mouse models of the disease. This treatment preserves the production of natural and potentially protective anti-oxidized low-density lipoprotein (oxLDL) IgM autoantibodies over IgG type anti-oxLDL antibodies, and markedly reduces pathogenic T cell activation. B cell depletion diminished T cell-derived IFN-gamma secretion and enhanced production of IL-17; neutralization of the latter abrogated CD20 antibody-mediated atheroprotection. These results challenge the current paradigm that B cell activation plays an overall protective role in atherogenesis and identify new antiatherogenic strategies based on B cell modulation.
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Ait-Oufella, H., Herbin, O., Bouaziz, J.-D., Binder, C. J., Uyttenhove, C., Laurans, L., Taleb, S., Van Vre, E., Esposito, B., Vilar, J., Sirvent, J., Van Snick, J., Tedgui, A., Tedder, T. F., & Mallat, Z. (2010). B cell depletion reduces the development of atherosclerosis in mice. The Journal of Experimental Medicine, 207(8), 1579-1587. https://doi.org/10.1084/jem.20100155 (Original work published 2010)