Inhibitory effect on arterial injury-induced neointimal formation by adoptive B-cell transfer in Rag-1 knockout mice.
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] mm(2), 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] mm(2), 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] mm(2), 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] mm(2), 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.
Dimayuga
Paul
P
Experimental Cardiovascular Research, Department of Medicine, Lund University, University Hospital MAS, Malmö, Sweden. DimayugaP@cshs.org
Cercek
Bojan
B
Oguchi
Sumito
S
Fredrikson
Gunilla Nordin
GN
Yano
Juliana
J
Shah
Prediman K
PK
Jovinge
Stefan
S
Nilsson
Jan
J
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D002339:Carotid Arteries / Q000276:immunology / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D004032:Diet; D018398:Homeodomain Proteins / Q000187:drug effects; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D017539:Tunica Intima / Q000254:growth & development* / Q000276:immunology / Q000293:injuries
D018398:Homeodomain Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C064658:RAG-1 protein; D002784:Cholesterol