B Cell–Mediated Antigen Presentation through MHC Class II Is Dispensable for Atherosclerosis Progression

Williams, Jesse W.; Elvington, Andrew; Kessler, Skyler H.; Wohltmann, Mary; Wu, Gregory F.; Randolph, Gwendalyn J.

doi:10.4049/immunohorizons.1800015

Cited by 11 publications

(8 citation statements)

References 33 publications

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“…Our observation is in accordance with reports where anti-CD40 antibody treatment reduced atherosclerosis in LDLR −/− mice (72) and inhibition of Th1 responses reduced atherosclerosis in ApoE −/− mice (73). Recently, Wigren et al, and Williams et al, reported that global or B cell-specific deficiency of MHCII were associated with low level of total IgG and IgM as well as low or undetectable oxLDL specific antibodies (74,75), supporting our data by defining differential roles of a B cell-specific MHCII and CD40 in generation of plasma cells and antibodies. Interestingly, in contrast to increased atherosclerosis in MHCII −/− ApoE −/− double knockout mice (74), MHCII deficiency on B cells did not affect atherosclerosis in LDLR −/− mice despite large but incomplete reductions in MHCII in B cells (75); reductions resulted in reduced IgG1 and IgG2c but not IgG2b nor IgM.…”

Section: Discussionsupporting

confidence: 87%

“…Recently, Wigren et al, and Williams et al, reported that global or B cell-specific deficiency of MHCII were associated with low level of total IgG and IgM as well as low or undetectable oxLDL specific antibodies (74,75), supporting our data by defining differential roles of a B cell-specific MHCII and CD40 in generation of plasma cells and antibodies. Interestingly, in contrast to increased atherosclerosis in MHCII −/− ApoE −/− double knockout mice (74), MHCII deficiency on B cells did not affect atherosclerosis in LDLR −/− mice despite large but incomplete reductions in MHCII in B cells (75); reductions resulted in reduced IgG1 and IgG2c but not IgG2b nor IgM. Incomplete depletion of MHCII from B cells is known to lead to strong selection of escaped B cells where MHCII is not deleted in the activated and plasmablast compartments (76,77), which may partially explain the latter observation.…”

Section: Discussionsupporting

confidence: 87%

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B Cell and CD4 T Cell Interactions Promote Development of Atherosclerosis

et al. 2020

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Interaction between B and CD4 T cells is crucial for their optimal responses in adaptive immunity. Immune responses augmented by their partnership promote chronic inflammation. Here we report that interaction between B and CD4 T cells augments their atherogenicity to promote lipid-induced atherosclerosis. Genetic deletion of the gene encoding immunoglobulin mu (µ) heavy chain (µMT) in ApoE −/− mice resulted in global loss of B cells including those in atherosclerotic plaques, undetectable immunoglobulins and impaired germinal center formation. Despite unaffected numbers in the circulation and peripheral lymph nodes, CD4 T cells were also reduced in spleens as were activated and memory CD4 T cells. In hyperlipidemic µMT −/− ApoE −/− mice, B cell deficiency decreased atherosclerotic lesions, accompanied by absence of immunoglobulins and reduced CD4 T cell accumulation in lesions. Adoptive transfer of B cells deficient in either MHCII or co-stimulatory molecule CD40, molecules required for B and CD4 T cell interaction, into B cell-deficient µMT −/− ApoE −/− mice failed to increase atherosclerosis. In contrast, wildtype B cells transferred into µMT −/− ApoE −/− mice increased atherosclerosis and increased CD4 T cells in lesions including activated and memory CD4 T cells. Transferred B cells also increased their expression of atherogenic cytokines IL-1β, TGF-β, MCP-1, M-CSF, and MIF, with partial restoration of germinal centers and plasma immunoglobulins. Our study demonstrates that interaction between B and CD4 T cells utilizing MHCII and CD40 is essential to augment their function to increase atherosclerosis in hyperlipidemic mice. These findings suggest that targeting B cell and CD4 T cell interaction may be a therapeutic strategy to limit atherosclerosis progression.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 87%

B Cell and CD4 T Cell Interactions Promote Development of Atherosclerosis

et al. 2020

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“…Transfer of WT B cells led to a drastic increase in atherosclerosis due to the infiltration of activated CD4 T cells into atherosclerotic lesions; however, this effect was significantly reduced when MHC-II-deficient B cells were used for adoptive transfer [ 161 ]. In the study from Williams and colleagues, CD19 cre recombinase was used to either delete or overexpress MHC-II specifically in B cells from Ldlr −/− mice [ 162 ]. No difference in atherosclerotic lesion size nor in lesion immune cell content was observed.…”

Section: Antigen Presentation and Co-stimulatory Moleculesmentioning

confidence: 99%

Functional Role of B Cells in Atherosclerosis

Shelby

Mußbacher

Galkina

2021

Cells

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Atherosclerosis is a lipid-driven inflammatory disease of blood vessels, and both innate and adaptive immune responses are involved in its development. The impact of B cells on atherosclerosis has been demonstrated in numerous studies and B cells have been found in close proximity to atherosclerotic plaques in humans and mice. B cells exert both atheroprotective and pro-atherogenic functions, which have been associated with their B cell subset attribution. While B1 cells and marginal zone B cells are considered to protect against atherosclerosis, follicular B cells and innate response activator B cells have been shown to promote atherosclerosis. In this review, we shed light on the role of B cells from a different, functional perspective and focus on the three major B cell functions: antibody production, antigen presentation/T cell interaction, and the release of cytokines. All of these functions have the potential to affect atherosclerosis by multiple ways and are dependent on the cellular milieu and the activation status of the B cell. Moreover, we discuss B cell receptor signaling and the mechanism of B cell activation under atherosclerosis-prone conditions. By summarizing current knowledge of B cells in and beyond atherosclerosis, we are pointing out open questions and enabling new perspectives.

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“…Mouse models showed that the depletion of B-cells attenuates plaque development. This suggests that antigen presentation of B-cells can promote atherosclerotic progression [58]. Indeed, differential effects of different B-cell subsets exist.…”

Section: Essential Mechanisms Promoting Vulnerabilitymentioning

confidence: 99%

Immune-Mediated Inflammation in Vulnerable Atherosclerotic Plaques

Mangge

Almer

2019

Molecules

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Atherosclerosis is a chronic long-lasting vascular disease leading to myocardial infarction and stroke. Vulnerable atherosclerotic (AS) plaques are responsible for these life-threatening clinical endpoints. To more successfully work against atherosclerosis, improvements in early diagnosis and treatment of AS plaque lesions are required. Vulnerable AS plaques are frequently undetectable by conventional imaging because they are non-stenotic. Although blood biomarkers like lipids, C-reactive protein, interleukin-6, troponins, and natriuretic peptides are in pathological ranges, these markers are insufficient in detecting the critical perpetuation of AS anteceding endpoints. Thus, chances to treat the patient in a preventive way are wasted. It is now time to solve this dilemma because clear results indicate a benefit of anti-inflammatory therapy per se without modification of blood lipids (CANTOS Trial, NCT01327846). This fact identifies modulation of immune-mediated inflammation as a new promising point of action for the eradication of fatal atherosclerotic endpoints.

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B Cell–Mediated Antigen Presentation through MHC Class II Is Dispensable for Atherosclerosis Progression

Cited by 11 publications

References 33 publications

B Cell and CD4 T Cell Interactions Promote Development of Atherosclerosis

B Cell and CD4 T Cell Interactions Promote Development of Atherosclerosis

Functional Role of B Cells in Atherosclerosis

Immune-Mediated Inflammation in Vulnerable Atherosclerotic Plaques

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