Abstract 633: B Cells in Artery Tertiary Lymphoid Organs of Aged Apolipoprotein-e Deficient Mice
Background: Atherosclerosis is recognized as a chronic in[[Unable to Display Character: ﬂ]]ammatory disease of arteries characterized by accumulation of in[[Unable to Display Character: ﬂ]]ammatory cells in the inner layer of the arterial wall, i.e. the intima. Though adaptive immune responses play important roles in all stages of atherosclerosis, the role of B cells is controversial as both atheroprotective and atherogenic effects have been reported. Moreover, information on B cells in the arterial wall is limited. We observed well-structured T and B cell aggregates in the adventitia of aorta segments adjacent to atherosclerotic lesions of aged Apolipoprotein-E Deficient (ApoE-/-) mice and referred to these structures as artery tertiary lymphoid organs (ATLOs).
Methods and Results: To understand atherosclerosis-associated B cell responses better, we undertook to delineate the B cell response in ATLOs versus secondary lymphoid organs. In ATLOs, marked numbers of germinal centre (GC) B cells, mantle zone B cells, and plasma cells were observed. Surprisingly, high numbers of B-1 B cells (20% per total B cells in ATLOs) were identified with B-1b cells making up 80% per total B-1 cells. The accumulation of B-1b cells in the diseased aorta was atherosclerosis-specific as the B-1b/B-1a ratio in ATLOs was increased when compared with the ratio in the peritoneal cavity (the major location of B-1 cells in mice), the spleen, and renal lymph nodes of Wt and ApoE-/- mice. ATLOs contained ~10% of GL-7+, PNA+ GC B cells per total IgD- B cells. The IgG1+ memory B cell percentage among total IgD- B cells was significantly increased, the IgM+/IgD+ (naïve B cells) percentage was significantly decreased, and the IgM-/IgD- percentage was significantly increased in ATLOs when compared with spleen, renal lymph nodes, and blood of aged Wt and ApoE-/- mice. Adoptive B-2 B cell transfer experiments revealed that B cell recruitment into ATLOs was specific, rapid, and highly regulated. Constitutively IgM and IgG antibody secreting cells were observed in ATLOs by ELISPOT.
Conclusion: Adventitial B cell aggregates were associated with marked expression of the B lymphocyte chemoattractant CXCL13. Our data indicate that ATLOs are a major site where adaptive and innate B cell immune responses are carried out in atherosclerosis.
Author Disclosures: P. Srikakulapu: None. S. Bontha: None. D. Hu: None. C. McNamara: None. A. Habenicht: None.
- © 2015 by American Heart Association, Inc.