title: Atherosclerosis Susceptibility in Mice Is Independent of the V1 Immunoglobulin Heavy Chain Gene.
abstract: OBJECTIVE
  The V1 (VHS107.1.42) immunoglobulin heavy chain gene is thought to be critical in producing IgM natural antibodies of the T15-idiotype that protect against both atherosclerosis and infection from Streptococcus pneumoniae. Our aim was to determine whether genetic loss of the V1 gene increased atherosclerotic plaque burden in vivo because of a reduction in the T15-idiotype or other atheroprotective antibodies.
  
  
  RESULTS
  We crossed VHS107.1.42-deficient mice with the atherosclerosis-prone Apoe(-/-) and Ldlr(-/-) strains. Although these double knockout strains manifested no defects in B-cell development, we did observe a substantial reduction in early immune responses against phosphocholine after immunization. However, the titers of plasma antibodies reacting against defined atherosclerotic antigens such as oxidized low-density lipoprotein, as well as the T15-idiotype, were unaffected by loss of the VHS107.1.42 gene in hypercholesterolemic mice. Furthermore, we observed no increase in atherosclerotic lesion formation, either within the aortic arch or aortic root. Robust deposition of IgM within atherosclerotic plaques could also be readily observed in both control and experimental mice.
  
  
  CONCLUSIONS
  Our data indicate that IgM-dependent protection against atherosclerosis is unlikely to be dependent on antibodies that use the VHS107.1.42 gene, in contrast to the acute immune response conferred by this heavy chain in the response to phosphocholine and in providing resistance against lethal S pneumoniae infection.
authors.affiliation: From the Department of Medicine and Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.C., D.N., K.A.P., D.K.J., G.K.H., D.F.J.K., S.M.); CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (S.G., C.J.B.); and Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria (S.G., C.J.B.).
authors.forename: Monica
authors.initials: M
authors.lastname: Centa
authors.affiliation: From the Department of Medicine and Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.C., D.N., K.A.P., D.K.J., G.K.H., D.F.J.K., S.M.); CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (S.G., C.J.B.); and Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria (S.G., C.J.B.).
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gruber
authors.affiliation: From the Department of Medicine and Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.C., D.N., K.A.P., D.K.J., G.K.H., D.F.J.K., S.M.); CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (S.G., C.J.B.); and Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria (S.G., C.J.B.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Nilsson
authors.affiliation: From the Department of Medicine and Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.C., D.N., K.A.P., D.K.J., G.K.H., D.F.J.K., S.M.); CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (S.G., C.J.B.); and Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria (S.G., C.J.B.).
authors.forename: Konstantinos A
authors.initials: KA
authors.lastname: Polyzos
authors.affiliation: From the Department of Medicine and Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.C., D.N., K.A.P., D.K.J., G.K.H., D.F.J.K., S.M.); CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (S.G., C.J.B.); and Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria (S.G., C.J.B.).
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Johansson
authors.affiliation: From the Department of Medicine and Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.C., D.N., K.A.P., D.K.J., G.K.H., D.F.J.K., S.M.); CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (S.G., C.J.B.); and Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria (S.G., C.J.B.).
authors.forename: Göran K
authors.initials: GK
authors.lastname: Hansson
authors.affiliation: From the Department of Medicine and Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.C., D.N., K.A.P., D.K.J., G.K.H., D.F.J.K., S.M.); CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (S.G., C.J.B.); and Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria (S.G., C.J.B.).
authors.forename: Daniel F J
authors.initials: DF
authors.lastname: Ketelhuth
authors.affiliation: From the Department of Medicine and Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.C., D.N., K.A.P., D.K.J., G.K.H., D.F.J.K., S.M.); CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (S.G., C.J.B.); and Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria (S.G., C.J.B.).
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
authors.affiliation: From the Department of Medicine and Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.C., D.N., K.A.P., D.K.J., G.K.H., D.F.J.K., S.M.); CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (S.G., C.J.B.); and Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria (S.G., C.J.B.). Stephen.malin@ki.se.
authors.forename: Stephen
authors.initials: S
authors.lastname: Malin
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D050438:Genes, Immunoglobulin Heavy Chain; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism; D056724:Immunity, Humoral; D007075:Immunoglobulin M / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010767:Phosphorylcholine / Q000276:immunology; D058226:Plaque, Atherosclerotic; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein; D010767:Phosphorylcholine
keywords: B-lymphocytes; aorta; atherosclerosis; mice; phosphorylcholine; thoracic