4684189_monash_128302.pdf (9.73 MB)
Role of B1a and B2 B lymphocytes in atherosclerosis
thesisposted on 2017-02-23, 03:09 authored by Tay, Christopher Jian Wei
B cells constitute a major component of the immune system. They have significant roles in many immune diseases. There are multiple subtypes of B cells. B1a and conventional B2 cells are the two main subsets. B1a cells are the primary producers of natural IgM antibodies while B2 cells are the primary producers of IgG antibodies. IgM and IgG antibodies are believed to protect and aggravate atherosclerosis respectively. Atherosclerosis is a chronic inflammatory disease that is characterised by focal accumulation of lipids and immune cells in the walls of medium and large arteries. It results in cardiovascular diseases which are the leading causes of death from heart attacks and strokes in the world. Current treatment is restricted to lipid-lowering statins which are not sufficient in preventing and remitting atherosclerosis. The differential roles of IgM and IgG antibodies in atherosclerosis suggest that B1a cells are atheroprotective and B2 cells are atherogenic. In this thesis, an atheroprotective effect of B1a cells was supported by increased atherosclerosis in ApoE-/- mice with diminished B1a cells after splenectomy. The aggravation of atherosclerosis in splenectomised ApoE-/- mice was markedly repressed by the reconstitution of B1a cells by adoptive transfer. On the other hand, an atherogenic effect of B2 cells was underscored by the exacerbation of atherosclerosis following their adoptive transfer into lymphocyte-deficient ApoE-/- Rag2-/- gamma c-chain-/- mice and B cell-deficient ApoE-/-uMT mice. Moreover, ApoE-/-BAFF-R-/- mice that were selectively deficient in B2 cells, but not B1a cells, had reduced atherosclerosis. These studies clearly indicate that B1a cells protect against atherosclerosis whereas B2 cells exacerbate atherosclerosis.