title: B1a B lymphocytes are atheroprotective by secreting natural IgM that increases IgM deposits and reduces necrotic cores in atherosclerotic lesions.
abstract: BACKGROUND
  Aggravated atherosclerosis in B lymphocyte-deficient chimeric mice and reduced atherosclerosis after transfer of unfractionated spleen B lymphocytes into splenectomized mice have led to the widely held notion that B lymphocytes are atheroprotective. However, B lymphocytes can be pathogenic, because their depletion by anti-CD20 antibody ameliorated atherosclerosis, and transfer of B2 lymphocytes aggravated atherosclerosis. These observations raise the question of the identity of the atheroprotective B-lymphocyte population.
  
  
  OBJECTIVE
  The purpose of the study was to identify an atheroprotective B-lymphocyte subset and mechanisms by which they confer atheroprotection.
  
  
  RESULTS
  Splenectomy of apolipoprotein E-deficient mice selectively reduced peritoneal B1a lymphocytes, plasma IgM, and oxidized low-density lipoprotein IgM levels and lesion IgM deposits. These reductions were accompanied by increased oil red O-stained atherosclerotic lesions and increased necrotic cores, oxidized low-density lipoproteins, and apoptotic cells in lesions. Plasma lipids, body weight, collagen, and smooth muscle content were unaffected. Transfer of B1a lymphocytes into splenectomized mice increased peritoneal B1a lymphocytes; restored plasma IgM, oxidized low-density lipoprotein IgM levels, and lesion IgM deposits; and potently attenuated atherosclerotic lesions, with reduced lesion necrotic cores, oxidized low-density lipoprotein, and apoptotic cells. In contrast, transfer of B1a lymphocytes that cannot secrete IgM failed to protect against atherosclerosis development in splenectomized mice despite reconstitution in the peritoneum.
  
  
  CONCLUSIONS
  B1a lymphocytes are an atheroprotective B-lymphocyte population. Our data suggest that natural IgM secreted by these lymphocytes offers protection by depositing IgM in atherosclerotic lesions, which reduces the necrotic cores of lesions.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Australia. tinsoe.kyaw@bakeridi.edu.au
authors.forename: Tin
authors.initials: T
authors.lastname: Kyaw
authors.forename: Christopher
authors.initials: C
authors.lastname: Tay
authors.forename: Surendran
authors.initials: S
authors.lastname: Krishnamurthi
authors.forename: Peter
authors.initials: P
authors.lastname: Kanellakis
authors.forename: Alex
authors.initials: A
authors.lastname: Agrotis
authors.forename: Peter
authors.initials: P
authors.lastname: Tipping
authors.forename: Alex
authors.initials: A
authors.lastname: Bobik
authors.forename: Ban-Hock
authors.initials: BH
authors.lastname: Toh
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis; D013156:Splenectomy; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D007075:Immunoglobulin M; C033027:secretory IgM