Perivascular adipose tissue harbors atheroprotective IgM-producing B cells

Prasad Srikakulapu, Aditi Upadhye, Sam M. Rosenfeld, Melissa A. Marshall, Chantel McSkimming, Alexandra W. Hickman, Ileana S. Mauldin, Gorav Ailawadi, M. Beatriz S. Lopes, Angela M. Taylor, Coleen A. McNamara

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Adipose tissue surrounding major arteries (Perivascular adipose tissue or PVAT) has long been thought to exist to provide vessel support and insulation. Emerging evidence suggests that PVAT regulates artery physiology and pathology, such as, promoting atherosclerosis development through local production of inflammatory cytokines. Yet the immune subtypes in PVAT that regulate inflammation are poorly characterized. B cells have emerged as important immune cells in the regulation of visceral adipose tissue inflammation and atherosclerosis. B cell-mediated effects on atherosclerosis are subset-dependent with B-1 cells attenuating and B-2 cells aggravating atherosclerosis. While mechanisms whereby B-2 cells aggravate atherosclerosis are less clear, production of immunoglobulin type M (IgM) antibodies is thought to be a major mechanism whereby B-1 cells limit atherosclerosis development. B-1 cell-derived IgM to oxidation specific epitopes (OSE) on low density lipoproteins (LDL) blocks oxidized LDL-induced inflammatory cytokine production and foam cell formation. However, whether PVAT contains B-1 cells and whether atheroprotective IgM is produced in PVAT is unknown. Results of the present study provide clear evidence that the majority of B cells in and around the aorta are derived from PVAT. Interestingly, a large proportion of these B cells belong to the B-1 subset with the B-1/B-2 ratio being 10-fold higher in PVAT relative to spleen and bone marrow. Moreover, PVAT contains significantly greater numbers of IgM secreting cells than the aorta. ApoE -/- mice with B cell-specific knockout of the gene encoding the helix-loop-helix factor Id3, known to have attenuated diet-induced atherosclerosis, have increased numbers of B-1b cells and increased IgM secreting cells in PVAT relative to littermate controls. Immunostaining of PVAT on human coronary arteries identified fat associated lymphoid clusters (FALCs) harboring high numbers of B cells, and flow cytometry demonstrated the presence of T cells and B cells including B-1 cells. Taken together, these results provide evidence that murine and human PVAT harbor B-1 cells and suggest that local IgM production may serve to provide atheroprotection.

Original languageEnglish (US)
Article number719
JournalFrontiers in Physiology
Volume8
Issue numberSEP
DOIs
StatePublished - Sep 22 2017

Fingerprint

Immunoglobulin M
Adipose Tissue
B-Lymphocytes
Atherosclerosis
Antibody-Producing Cells
Aorta
Arteries
Cytokines
Inflammation
Foam Cells
Gene Knockout Techniques
Intra-Abdominal Fat
Apolipoproteins E
LDL Lipoproteins
Epitopes
Coronary Vessels
Flow Cytometry
Spleen
Bone Marrow
Fats

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Srikakulapu, P., Upadhye, A., Rosenfeld, S. M., Marshall, M. A., McSkimming, C., Hickman, A. W., ... McNamara, C. A. (2017). Perivascular adipose tissue harbors atheroprotective IgM-producing B cells. Frontiers in Physiology, 8(SEP), [719]. https://doi.org/10.3389/fphys.2017.00719

Perivascular adipose tissue harbors atheroprotective IgM-producing B cells. / Srikakulapu, Prasad; Upadhye, Aditi; Rosenfeld, Sam M.; Marshall, Melissa A.; McSkimming, Chantel; Hickman, Alexandra W.; Mauldin, Ileana S.; Ailawadi, Gorav; Lopes, M. Beatriz S.; Taylor, Angela M.; McNamara, Coleen A.

In: Frontiers in Physiology, Vol. 8, No. SEP, 719, 22.09.2017.

Research output: Contribution to journalArticle

Srikakulapu, P, Upadhye, A, Rosenfeld, SM, Marshall, MA, McSkimming, C, Hickman, AW, Mauldin, IS, Ailawadi, G, Lopes, MBS, Taylor, AM & McNamara, CA 2017, 'Perivascular adipose tissue harbors atheroprotective IgM-producing B cells', Frontiers in Physiology, vol. 8, no. SEP, 719. https://doi.org/10.3389/fphys.2017.00719
Srikakulapu P, Upadhye A, Rosenfeld SM, Marshall MA, McSkimming C, Hickman AW et al. Perivascular adipose tissue harbors atheroprotective IgM-producing B cells. Frontiers in Physiology. 2017 Sep 22;8(SEP). 719. https://doi.org/10.3389/fphys.2017.00719
Srikakulapu, Prasad ; Upadhye, Aditi ; Rosenfeld, Sam M. ; Marshall, Melissa A. ; McSkimming, Chantel ; Hickman, Alexandra W. ; Mauldin, Ileana S. ; Ailawadi, Gorav ; Lopes, M. Beatriz S. ; Taylor, Angela M. ; McNamara, Coleen A. / Perivascular adipose tissue harbors atheroprotective IgM-producing B cells. In: Frontiers in Physiology. 2017 ; Vol. 8, No. SEP.
@article{a69361cdc5224643a11f24b36a6c7804,
title = "Perivascular adipose tissue harbors atheroprotective IgM-producing B cells",
abstract = "Adipose tissue surrounding major arteries (Perivascular adipose tissue or PVAT) has long been thought to exist to provide vessel support and insulation. Emerging evidence suggests that PVAT regulates artery physiology and pathology, such as, promoting atherosclerosis development through local production of inflammatory cytokines. Yet the immune subtypes in PVAT that regulate inflammation are poorly characterized. B cells have emerged as important immune cells in the regulation of visceral adipose tissue inflammation and atherosclerosis. B cell-mediated effects on atherosclerosis are subset-dependent with B-1 cells attenuating and B-2 cells aggravating atherosclerosis. While mechanisms whereby B-2 cells aggravate atherosclerosis are less clear, production of immunoglobulin type M (IgM) antibodies is thought to be a major mechanism whereby B-1 cells limit atherosclerosis development. B-1 cell-derived IgM to oxidation specific epitopes (OSE) on low density lipoproteins (LDL) blocks oxidized LDL-induced inflammatory cytokine production and foam cell formation. However, whether PVAT contains B-1 cells and whether atheroprotective IgM is produced in PVAT is unknown. Results of the present study provide clear evidence that the majority of B cells in and around the aorta are derived from PVAT. Interestingly, a large proportion of these B cells belong to the B-1 subset with the B-1/B-2 ratio being 10-fold higher in PVAT relative to spleen and bone marrow. Moreover, PVAT contains significantly greater numbers of IgM secreting cells than the aorta. ApoE -/- mice with B cell-specific knockout of the gene encoding the helix-loop-helix factor Id3, known to have attenuated diet-induced atherosclerosis, have increased numbers of B-1b cells and increased IgM secreting cells in PVAT relative to littermate controls. Immunostaining of PVAT on human coronary arteries identified fat associated lymphoid clusters (FALCs) harboring high numbers of B cells, and flow cytometry demonstrated the presence of T cells and B cells including B-1 cells. Taken together, these results provide evidence that murine and human PVAT harbor B-1 cells and suggest that local IgM production may serve to provide atheroprotection.",
author = "Prasad Srikakulapu and Aditi Upadhye and Rosenfeld, {Sam M.} and Marshall, {Melissa A.} and Chantel McSkimming and Hickman, {Alexandra W.} and Mauldin, {Ileana S.} and Gorav Ailawadi and Lopes, {M. Beatriz S.} and Taylor, {Angela M.} and McNamara, {Coleen A.}",
year = "2017",
month = "9",
day = "22",
doi = "10.3389/fphys.2017.00719",
language = "English (US)",
volume = "8",
journal = "Frontiers in Physiology",
issn = "1664-042X",
publisher = "Frontiers Research Foundation",
number = "SEP",

}

TY - JOUR

T1 - Perivascular adipose tissue harbors atheroprotective IgM-producing B cells

AU - Srikakulapu, Prasad

AU - Upadhye, Aditi

AU - Rosenfeld, Sam M.

AU - Marshall, Melissa A.

AU - McSkimming, Chantel

AU - Hickman, Alexandra W.

AU - Mauldin, Ileana S.

AU - Ailawadi, Gorav

AU - Lopes, M. Beatriz S.

AU - Taylor, Angela M.

AU - McNamara, Coleen A.

PY - 2017/9/22

Y1 - 2017/9/22

N2 - Adipose tissue surrounding major arteries (Perivascular adipose tissue or PVAT) has long been thought to exist to provide vessel support and insulation. Emerging evidence suggests that PVAT regulates artery physiology and pathology, such as, promoting atherosclerosis development through local production of inflammatory cytokines. Yet the immune subtypes in PVAT that regulate inflammation are poorly characterized. B cells have emerged as important immune cells in the regulation of visceral adipose tissue inflammation and atherosclerosis. B cell-mediated effects on atherosclerosis are subset-dependent with B-1 cells attenuating and B-2 cells aggravating atherosclerosis. While mechanisms whereby B-2 cells aggravate atherosclerosis are less clear, production of immunoglobulin type M (IgM) antibodies is thought to be a major mechanism whereby B-1 cells limit atherosclerosis development. B-1 cell-derived IgM to oxidation specific epitopes (OSE) on low density lipoproteins (LDL) blocks oxidized LDL-induced inflammatory cytokine production and foam cell formation. However, whether PVAT contains B-1 cells and whether atheroprotective IgM is produced in PVAT is unknown. Results of the present study provide clear evidence that the majority of B cells in and around the aorta are derived from PVAT. Interestingly, a large proportion of these B cells belong to the B-1 subset with the B-1/B-2 ratio being 10-fold higher in PVAT relative to spleen and bone marrow. Moreover, PVAT contains significantly greater numbers of IgM secreting cells than the aorta. ApoE -/- mice with B cell-specific knockout of the gene encoding the helix-loop-helix factor Id3, known to have attenuated diet-induced atherosclerosis, have increased numbers of B-1b cells and increased IgM secreting cells in PVAT relative to littermate controls. Immunostaining of PVAT on human coronary arteries identified fat associated lymphoid clusters (FALCs) harboring high numbers of B cells, and flow cytometry demonstrated the presence of T cells and B cells including B-1 cells. Taken together, these results provide evidence that murine and human PVAT harbor B-1 cells and suggest that local IgM production may serve to provide atheroprotection.

AB - Adipose tissue surrounding major arteries (Perivascular adipose tissue or PVAT) has long been thought to exist to provide vessel support and insulation. Emerging evidence suggests that PVAT regulates artery physiology and pathology, such as, promoting atherosclerosis development through local production of inflammatory cytokines. Yet the immune subtypes in PVAT that regulate inflammation are poorly characterized. B cells have emerged as important immune cells in the regulation of visceral adipose tissue inflammation and atherosclerosis. B cell-mediated effects on atherosclerosis are subset-dependent with B-1 cells attenuating and B-2 cells aggravating atherosclerosis. While mechanisms whereby B-2 cells aggravate atherosclerosis are less clear, production of immunoglobulin type M (IgM) antibodies is thought to be a major mechanism whereby B-1 cells limit atherosclerosis development. B-1 cell-derived IgM to oxidation specific epitopes (OSE) on low density lipoproteins (LDL) blocks oxidized LDL-induced inflammatory cytokine production and foam cell formation. However, whether PVAT contains B-1 cells and whether atheroprotective IgM is produced in PVAT is unknown. Results of the present study provide clear evidence that the majority of B cells in and around the aorta are derived from PVAT. Interestingly, a large proportion of these B cells belong to the B-1 subset with the B-1/B-2 ratio being 10-fold higher in PVAT relative to spleen and bone marrow. Moreover, PVAT contains significantly greater numbers of IgM secreting cells than the aorta. ApoE -/- mice with B cell-specific knockout of the gene encoding the helix-loop-helix factor Id3, known to have attenuated diet-induced atherosclerosis, have increased numbers of B-1b cells and increased IgM secreting cells in PVAT relative to littermate controls. Immunostaining of PVAT on human coronary arteries identified fat associated lymphoid clusters (FALCs) harboring high numbers of B cells, and flow cytometry demonstrated the presence of T cells and B cells including B-1 cells. Taken together, these results provide evidence that murine and human PVAT harbor B-1 cells and suggest that local IgM production may serve to provide atheroprotection.

UR - http://www.scopus.com/inward/record.url?scp=85029703416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029703416&partnerID=8YFLogxK

U2 - 10.3389/fphys.2017.00719

DO - 10.3389/fphys.2017.00719

M3 - Article

VL - 8

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

IS - SEP

M1 - 719

ER -