Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice
Giuseppina Caligiuri, … , Bruno Poirier, Göran K. Hansson
Giuseppina Caligiuri, … , Bruno Poirier, Göran K. Hansson
Published March 15, 2002
Citation Information: J Clin Invest. 2002;109(6):745-753. https://doi.org/10.1172/JCI7272.
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Article

Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice

Abstract

Atherosclerosis is characterized by vascular inflammation and associated with systemic and local immune responses to oxidized LDL (oxLDL) and other antigens. Since immunization with oxLDL reduces atherosclerosis, we hypothesized that the disease might be associated with development of protective immunity. Here we show that spleen-associated immune activity protects against atherosclerosis. Splenectomy dramatically aggravated atherosclerosis in hypercholesterolemic apoE knockout (apoE°) mice. Transfer of spleen cells from atherosclerotic apoE° mice significantly reduced disease development in young apoE° mice. To identify the protective subset, donor spleen cells were divided into B and T cells by immunomagnetic separation before transfer. Protection was conferred by B cells, which reduced disease in splenectomized apoE° mice to one-fourth of that in splenectomized apoE° controls. Protection could also be demonstrated in intact, nonsplenectomized mice and was associated with an increase in antibody titers to oxLDL. Fewer CD4+ T cells were found in lesions of protected mice, suggesting a role for T-B cell cooperation. These results demonstrate that B cell–associated protective immunity develops during atherosclerosis and reduces disease progression.

Authors

Giuseppina Caligiuri, Antonino Nicoletti, Bruno Poirier, Göran K. Hansson

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Figure 1

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Effect of splenectomy and cell transfer on atherosclerotic lesions in ap...
Effect of splenectomy and cell transfer on atherosclerotic lesions in apoE° mice. Morphometric analysis of lesion size (cross-section area at the aortic root occupied by lesion, ×103μm2, mean ± SEM). Data are from a representative experiment, and additional data summarizing all experiments are displayed in Table 1. (a) Splenectomy (Sx) increases lesion formation. Lesion size 12 weeks after Sx was significantly increased (P < 0.05, n = 6 per group) when compared with sham-operated apoE° mice. (b) Transfer (Trf) of B cells but not T cells from atherosclerotic apoE° mice reduces lesion formation in sham-operated apoE° mice. Lesions in the latter (n = 6) were significantly larger than those in B cell–transferred mice (P < 0.05, n = 7) but not different from those in T cell–transferred ones (n = 5). (c) Spleen cell transfer rescues apoE° mice from the proatherogenic effect of splenectomy. Average lesion sizes are shown for sham-operated (n = 8) and Sx (n = 7) apoE° mice, and for Sx apoE° mice who received spleen cell transfer from young apoE° mice (yng E°, n = 4 recipients), wild-type C57BL/6J mice (E+, n = 4), or atherosclerotic apoE° mice (ascl E°, n = 6) or purified spleen T cells (E° T, n = 4 recipients) or B cells (E° B, n = 4) from atherosclerotic apoE° mice. *Significantly different from sham, P < 0.05; ‡significantly different from Sx, P < 0.05. Op, operation.