title: BAFF receptor mAb treatment ameliorates development and progression of atherosclerosis in hyperlipidemic ApoE(-/-) mice.
abstract: OBJECTIVE
  Option to attenuate atherosclerosis by depleting B2 cells is currently limited to anti-CD20 antibodies which deplete all B-cell subtypes. In the present study we evaluated the capacity of a monoclonal antibody to B cell activating factor-receptor (BAFFR) to selectively deplete atherogenic B2 cells to prevent both development and progression of atherosclerosis in the ApoE(-/-) mouse.
  
  
  RESULTS
  To determine whether the BAFFR antibody prevents atherosclerosis development, we treated ApoE(-/-) mice with the antibody while feeding them a high fat diet (HFD) for 8 weeks. Mature CD93(-) CD19(+) B2 cells were reduced by treatment, spleen B-cell zones disrupted and spleen CD20 mRNA expression decreased while B1a cells and non-B cells were spared. Atherosclerosis was ameliorated in the hyperlipidemic mice and CD19(+) B cells, CD4(+) and CD8(+) T cells were reduced in atherosclerotic lesions. Expressions of proinflammatory cytokines, IL1β, TNFα, and IFNγ in the lesions were also reduced, while MCP1, MIF and VCAM-1 expressions were unaffected. Plasma immunoglobulins were reduced, but MDA-oxLDL specific antibodies were unaffected. To determine whether anti-BAFFR antibody ameliorates progression of atherosclerosis, we first fed ApoE(-/-) mice a HFD for 6 weeks, and then instigated anti-BAFFR antibody treatment for a further 6 week-HFD. CD93(-) CD19(+) B2 cells were selectively decreased and atherosclerotic lesions were reduced by this treatment.
  
  
  CONCLUSIONS
  Anti-BAFFR monoclonal antibody selectively depletes mature B2 cells while sparing B1a cells, disrupts spleen B-cell zones and ameliorates atherosclerosis development and progression in hyperlipidemic ApoE(-/-) mice. Our findings have potential for clinical translation to manage atherosclerosis-based cardiovascular diseases.
authors.affiliation: Vascular Biology and Atherosclerosis Laboratory Baker IDI Heart and Diabetes Institute, Victoria, Australia. tinsoe.kyaw@bakeridi.edu.au
authors.forename: Tin
authors.initials: T
authors.lastname: Kyaw
authors.forename: Peng
authors.initials: P
authors.lastname: Cui
authors.forename: Christopher
authors.initials: C
authors.lastname: Tay
authors.forename: Peter
authors.initials: P
authors.lastname: Kanellakis
authors.forename: Hamid
authors.initials: H
authors.lastname: Hosseini
authors.forename: Edgar
authors.initials: E
authors.lastname: Liu
authors.forename: Antonius G
authors.initials: AG
authors.lastname: Rolink
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; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D053265:B-Cell Activation Factor Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D059305:Diet, High-Fat; D018450:Disease Progression; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001057:Apolipoproteins E; D053265:B-Cell Activation Factor Receptor; D016207:Cytokines; C486662:Tnfrsf13c protein, mouse
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