Limiting Lesions

Science Signaling  10 Aug 2010:
Vol. 3, Issue 134, pp. ec245
DOI: 10.1126/scisignal.3134ec245

B cells, unlike other elements of the immune response, have been thought to protect against development of atherosclerosis, a matter of concern in light of the use of targeted therapies aimed at decreasing the number of mature B cells in various immune-related disorders. Interested in exploring the role of B cells in atherosclerosis, Ait-Oufella et al. evaluated the effects of treatment with a monoclonal antibody directed against CD20 (CD20 mAb, used to deplete mature B cells) on development of atherosclerotic lesions in a mouse model [mice lacking apolipoprotein E (Apoe–/– mice) fed a high-fat diet]. Unexpectedly, they found that, although CD20 mAB failed to affect plasma cholesterol, it decreased lesion size. Similar effects of B cell depletion were apparent in another mouse model of atherosclerosis, mice lacking the low-density lipoprotein receptor. Further analysis of atherosclerotic lesions revealed a decrease in macrophage accumulation in the lesions of CD20 mAb-treated mice, as well as a decrease in the abundance of T cells and B cells. Spleen-derived CD4+ T cells from mice treated with CD20 mAb showed decreased activation and proliferation compared with those from untreated mice. Moreover, dendritic cells from CD20 mAb-treated mice showed decreased abundance of CD40 and were less effective than control dendritic cells at stimulating the in vitro proliferation of T cells from untreated mice. Cytokines derived from T cells affect the development of atherosclerotic lesions, and analyses of the cytokine profiles of purified T cells revealed changes consistent with the antiatherosclerotic effects of B cell depletion [decreased interferon-γ and increased interleukin 17 (IL-17) in T cells from B cell–depleted compared with control mice]. Indeed, administration of a neutralizing antibody directed against IL-17 concurrently with CD20 mAb blocked the atheroprotective effects of the latter. The authors thus conclude that B cell depletion is protective against atherosclerosis and that B cell manipulation might provide an antiatherogenic strategy.

H. Ait-Oufella, O. Herbin, J.-D. Bouaziz, C. J. Binder, C. Uyttenhove, L. Laurans, S. Taleb, E. Van Vré, B. Esposito, J. Vilar, J. Sirvent, J. Van Snick, A. Tedgui, T. F. Tedder, Z. Mallat, B cell depletion reduces the development of atherosclerosis in mice. J. Exp. Med. 207, 1579–1587 (2010). [Abstract] [Full Text]