on February 7, 2002
Published online before print February 7, 2002, doi: 10.1161/01.ATV.0000012455.62765.BF
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Submitted on December 27, 2001
Accepted on January 16, 2002
Inhibitory Effect on Arterial Injury-Induced Neointimal Formation by Adoptive B-Cell Transfer in Rag-1 Knockout Mice
Paul Dimayuga *;
From Experimental Cardiovascular Research (P.D., G.N.F., S.J., J.N.), Department of Medicine, Lund University, University Hospital MAS, Malmö, Sweden; the Atherosclerosis Research Center (P.D., B.C., S.O., J.Y., P.K.S.), Burns and Allen Research Institute, Division of Cardiology, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, Calif; and the Department of Biomedical Laboratory Science, Health, and Society (G.N.F.), Malmö University, Malmö, Sweden.
* To whom correspondence should be addressed. E-mail: DimayugaP{at}cshs.org.
Abstract—We investigated the effect of B-cell reconstitution in immune-deficient Rag-1 knockout (KO) mice subjected to arterial injury. After 21 days, injury induced a 4- to 5-fold increase in neointimal formation in Rag-1 KO mice fed normal chow compared with wild-type (WT) mice (0.020±0.0160 [n=8] versus 0.0049±0.0022 [n=8] mm2, respectively; P<0.05) and in western-type diet--fed Rag-1 KO mice compared with WT mice (0.0312±0.0174 [n=7] versus 0.0050±0.0028 [n=6] mm2, respectively; P<0.05). To investigate the role of B cells in response to injury, Rag-1 KO mice were reconstituted with B cells derived from the spleens of WT mice, with donors and recipients on the same diet. Reconstitution of Rag-1 KO mice with B cells from WT mice (both fed normal chow) reduced neointimal formation compared with the effect in unreconstituted Rag-1 KO mice (0.0076±0.0039 [n=9] versus 0.020±0.0160 [n=8] mm2, respectively; P<0.05). Reconstitution of Rag-1 KO mice with B cells from WT mice (both fed a western diet) reduced neointimal formation compared the effect in Rag-1 KO mice (0.0087±0.0037 [n=8] versus 0.0312±0.0174 [n=7] mm2, respectively; P<0.05). Injured carotid arteries from reconstituted Rag-1 KO mice had detectable IgM and IgG, indicating viable transfer of B cells. The results suggest that B cells modulate the response to arterial injury.
Key words: neointima • B cells • arterial injury • Rag-1 knockout mice