Alterations in the frequency and phenotype of B cells during experimental atherosclerosis are associated with hipercholesterolemia
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1
Universidad de Antioquia UdeA, Instituto de Investigaciones Médicas, Facultad de Medicina, Colombia
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2
Universidad de Antioquia, Instituto de Investigaciones Médicas, Facultad de Medicina, Colombia
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3
Universidad CES, Facultad de Medicina, Colombia
Introduction
Atherosclerosis is a systemic inflammatory process considered the leading cause of cardiovascular diseases and characterized by lipid accumulation, infiltration of immune cells, and plaque formation in arterial intima. The main immune cells involved in the atherogenic process are the macrophages; however, other cells of the adaptive immune system such as T and B lymphocytes are also involved. B cells have been described mainly in the arterial adventitia, and there are evidences that suggest both have proatherogenic and atheroprotective roles. This dichotomy seemingly depends on the subpopulation involved, the previous antigenic contact, and the age of the mice. In addition, previous evidences have shown that the absence of B cells in the aortic tissue induces an increase in size of atherosclerotic lesions and in macrophage infiltration. However, the exact role of B cells in the immunopathology of atherosclerosis is not fully understood, neither if any B lymphocyte subset is altered in the course of the disease. Therefore, we studied the phenotype of B cells in apoE-/- mice with advanced atherosclerosis (fed with high fat diet, HFD) using a flow cytometry based approach.
Methods
Wild type and apolipoprotein-E-deficient (apoE-/-) mice of 8 weeks-old were fed for 12 weeks with a standard chow diet or HFD. ApoE-/- HFD mice develop advanced atherosclerosis. The frequency and phenotype of marginal zone (MZ), follicular (FO), transitional 1-like (T1-like) and 2 (T2), and CD5+ subpopulations of splenic and aortic B cells was evaluated by flow cytometry, according to the expression of CD5, CD19, CD21, CD23, CD24, CD40, CD80, CD86 and CD95. The intracellular lipid content was evaluated by Nile Red accumulation (mean fluorescence intensity, MFI) in splenic cells from young apoE-/- mice cultured under lipemic and non-lipemic serum.
Results
An increased frequency of B cells and lower expression of CD19 and CD21 was observed in splenocytes from mice with advanced atherosclerosis. A high frequency of T1-like and a low frequency of FO cells in apoE-/- HFD mice was found. There were no differences in the frequencies of T2, MZ and CD5+ subpopulations. In addition, B cells isolated from these mice had augmented expression of CD40, CD80, CD86 and CD95.
In aortas, a decrease in the frequency of B cells was observed in apoE-/- HFD mice. Similar to spleen, aortic B cells from these mice had lower expression of CD19 and a higher percentage of CD95+ cells. No differences in the frequency of B cell subsets were found among the study groups.
Significant correlations between CD19 expression on splenic and aortic B cells and serum cholesterol levels were found. To evaluate if the observed changes on B cells could be partly explained by dyslipidemia, splenocytes from young apoE-/- mice were cultured with lipemic and non-lipemic serum. Decreased CD19 expression and increased lipid content was observed in B cells from splenocytes cultured with lipemic serum.
Conclusions
B cells subpopulations from mice with established atherosclerosis (apoE-/- HFD) present alterations in their frequency and exhibit an activated profile, which could be related with dyslipidemia. We propose that the excess of circulating cholesterol could accumulate in B cells, which in turn may possibly affect different aspects of their biology.
Acknowledgements
This work received financial support by the grants (Colciencias project number 111554431390) and Programa de Sostenibilidad Universidad de Antioquia 2014-2015.
Keywords:
B cell,
Atherosclerosis,
Dyslipidemia,
Cholesterol,
Aorta,
Apolipoproteins E
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Oral Presentation
Topic:
Adaptive Immunity
Citation:
Rincón-Arévalo
H,
Castano
DM,
Villa-Pulgarín
J,
Ramírez-Pineda
JR,
Vásquez
G and
Yassin
L
(2015). Alterations in the frequency and phenotype of B cells during experimental atherosclerosis are associated with hipercholesterolemia.
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00321
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Received:
24 Apr 2015;
Published Online:
15 Sep 2015.
*
Correspondence:
Dr. Diana M Castano, Universidad de Antioquia UdeA, Instituto de Investigaciones Médicas, Facultad de Medicina, Medellin, Colombia, dmcastano@gmail.com
Dr. Lina Yassin, Universidad CES, Facultad de Medicina, Medellin, Colombia, yascatorce@yahoo.com