B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice.
OBJECTIVE
Atherosclerosis is an inflammatory disease characterized by innate and adaptive immune responses. We investigated the role of B cells and antibodies in the development of atherosclerosis in low density lipoprotein (LDL) receptor-deficient (LDLR(-/-)) mice.


RESULTS
Using wild-type and B cell-deficient mice as bone marrow donors, we were able to generate LDLR(-/-) mice that possessed <1.0% of their normal B cell population. B cell-deficient LDLR(-/-) mice on a Western diet showed marked decreases in total serum antibody and anti-oxidized LDL antibody. B cell deficiency was associated with a 30% to 40% increase in the lesion area in the proximal and distal aortas. Real-time reverse transcription-polymerase chain reaction and enzyme-linked immunospot analyses showed a decrease in proatherogenic (interferon-gamma) and antiatherogenic (interleukin-10 and transforming growth factor-beta) cytokine mRNA and a decrease in interleukin-4- and interferon-gamma-producing cells. Additionally, we observed a decrease in splenocyte proliferation to oxidized LDL in the B cell-deficient LDLR(-/-) mice, suggesting that B lymphocytes may play a role in the presentation of lipid antigen.


CONCLUSIONS
Collectively, these data demonstrate that B cells and/or antibodies are protective against atherosclerosis and that this protection may be conferred by B cell-mediated immune regulation.
Major
Amy S
AS
Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University, Nashville, Tenn 37232-6300, USA.
Fazio
Sergio
S
Linton
MacRae F
MF
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D005260:Female; D008077:Lipoproteins, LDL / Q000276:immunology; D008231:Lymphopenia / Q000097:blood / Q000150:complications / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics*; D013154:Spleen / Q000737:chemistry / Q000166:cytology; D014280:Triglycerides / Q000097:blood
D000906:Antibodies; D016207:Cytokines; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011973:Receptors, LDL; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D002784:Cholesterol