Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04
  • 2024-05

    • br Funding Sources This work was funded through institutiona

    2018-11-07


    Funding Sources This work was funded through institutional support from INSERM and by the Agence Nationale pour la Recherche (ANR Blanc 2011, No.: 11-BSV1 005 03, ANR-13-ISV1-0006-01), the Fondation pour la Recherche Médicale (DEQ20140329556), the Programme Hospitalier de Recherche Clinique (PHRC grant AOM 06179), and by grants from INSERM and Ministère Délégué à la Recherche et des Nouvelles Technologies.
    Conflict of Interest
    Author Contributions
    Introduction Atherosclerosis is a major cause of harm to human health and a leading pathological contributor to cardiovascular morbidity and mortality worldwide. Studies during the past decade have highlighted the important role of the immune system in atherosclerosis (Libby, 2002; Wick et al., 2004). Consequently, reducing the associated inflammation that sustains the immune response has become an important target for scientific and future therapeutic investigations because lipid control alone does not effectively prevent the progression of atherosclerosis in some patients (Hilgendorf et al., 2014). However, despite a long-known association with atherosclerosis, B cells and immunoglobulins, important components of the immune system, have received relatively little attention. In particular, the roles of B2 cells, which represent the vast majority of B cells, including follicular (FO) as well as marginal zone (MZ) B cells, remained largely unexplored (Doran et al., 2012; Kyaw et al., 2010; Lipinski et al., 2011). In general, FO B cells, which predominantly participate in T-cell-dependent (TD) antibody responses, might be endowed with proatherogenic potential (Nicoletti et al., 1998). In contrast to TD FO B cells, MZ B cells, situated peripherally to FO B cells, reside in the spleen (Victora, 2014), which serves as the interface with the circulation, and are located at the first line of defense against antigens (Martin and Kearney, 2002). MZ B cells predominantly give rise to rapid T-cell-independent (TI) antibody responses to antigens, producing TI K03861 Supplier (Puga et al., 2012). However, whether MZ B cells have atheroprotective properties similar to TI B cells (e.g., B1 cells) remains unknown (Ait-Oufella et al., 2010; Kyaw et al., 2011). The spleen, the largest immune organ in the periphery, is the major B2 B-cell reservoir, which harbors about 80% of FO B cells and 10% of MZ B cells among all splenic B cells (Tsiantoulas et al., 2014). However, it should be noted that spleen-associated immune activity protects against atherosclerosis (Emtiazy et al., 2013; Lammers et al., 2012; Rezende et al., 2011), and removal of the spleen, which results in accelerated atherosclerosis, has been shown to deplete B1a cells from the peritoneum, followed by a strong decrease in plasma immunoglobulin (Ig) M titers (Kyaw et al., 2011; Wardemann et al., 2002). Moreover, it should be emphasized that FO B cells and MZ B cells are also missing after splenectomy. In addition, at present, there is contradictory evidence concerning the role of B2 cells in atherogenesis after adoptive transfer of splenic B2 cells (Doran et al., 2012; Kyaw et al., 2010; Lipinski et al., 2011), and dissection of the functions of individual B2-cell subsets (MZ versus FO) and separation of the intrinsic biological properties of these B2 cells from effects mediated by the antibodies they secrete during atherogenesis have yet to be performed (Tsiantoulas et al., 2014). On the other hand, as one important source of antigens, recent studies have suggested that commensal microbes might exert a substantial impact on atherosclerosis (Brown and Hazen, 2015; Koren et al., 2011; Serino et al., 2014; Tang and Hazen, 2014). Remarkably, commensal microbes play an essential role in the activation of MZ B cells and B2 cell-mediated IgG antibody production (Balázs et al., 2002; Cerutti et al., 2012; Martin and Kearney, 2002; Puga et al., 2012; Vinuesa and Chang, 2013; Weill et al., 2009). However, whether these effects contribute to the development of atherosclerosis remains largely unexplored. In parallel with these findings, our previous clinical research revealed that many autoantibodies differing from those found in chronic autoimmune diseases are associated with atherosclerosis (Ishigami et al., 2013). Meanwhile, previous studies have reported that human antibodies cross-react with outer membrane proteins of bacteria as well as with proteins involved in atherogenesis (Canducci et al., 2012). However, the link between B2 cells and commensal microbes in the development of atherosclerosis has not yet been reported.