Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/49149
Title: The role of B cells in the Pathogenesis of Atherosclerosis
Authors: KHOO HAN BOON LAWRENCE
Keywords: B cells, antibodies, antibody-secreting cells, oxidized low-density lipoprotein, hypercholesterolemia, atherosclerosis
Issue Date: 17-Jul-2013
Source: KHOO HAN BOON LAWRENCE (2013-07-17). The role of B cells in the Pathogenesis of Atherosclerosis. ScholarBank@NUS Repository.
Abstract: The presence of modified self-lipid specific autoantibodies such as anti-oxidized low-density lipoprotein (oxLDL) has been reported in clinical and experimental atherosclerosis, implying the involvement of humoral B cell responses. We showed that atherosclerotic apoE-/- mice exhibited elevated circulating total and oxLDL-specific IgM autoantibodies, and increased plasma cells in spleen and lymph nodes. However, differential dominant antibody-producing pathways were observed in these lymphoid organs, namely: robust extrafollicular responses in spleen and increased germinal center reactions in lymph nodes. Further studies in apoE-/- mice indicated that spleen was the major source of elevated total and oxLDL-specific IgM autoantibodies in circulation. In parallel, we showed that splenic antibody-secreting cells migrated to the bone marrow for long-term maintenance. The IgM humoral response observed in apoE-/- mice was associated with hypercholesterolemia. Collectively, our findings suggests that hypercholesterolemia-associated splenic extrafollicular responses contribute to elevated total and oxLDL-specific IgM autoantibodies and are sustained by long-lived plasma cells in the bone marrow.
URI: http://scholarbank.nus.edu.sg/handle/10635/49149
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