B1a B lymphocytes are atheroprotective by secreting natural IgM that increases IgM deposits and reduces necrotic cores in atherosclerotic lesions.

Abstract

RATIONALE:

Aggravated atherosclerosis in B lymphocyte-deficient chimeric mice and reduced atherosclerosis after transfer of unfractionated spleen B lymphocytes into splenectomized mice have led to the widely held notion that B lymphocytes are atheroprotective. However, B lymphocytes can be pathogenic, because their depletion by anti-CD20 antibody ameliorated atherosclerosis, and transfer of B2 lymphocytes aggravated atherosclerosis. These observations raise the question of the identity of the atheroprotective B-lymphocyte population.

OBJECTIVE:

The purpose of the study was to identify an atheroprotective B-lymphocyte subset and mechanisms by which they confer atheroprotection.

METHODS AND RESULTS:

Splenectomy of apolipoprotein E-deficient mice selectively reduced peritoneal B1a lymphocytes, plasma IgM, and oxidized low-density lipoprotein IgM levels and lesion IgM deposits. These reductions were accompanied by increased oil red O-stained atherosclerotic lesions and increased necrotic cores, oxidized low-density lipoproteins, and apoptotic cells in lesions. Plasma lipids, body weight, collagen, and smooth muscle content were unaffected. Transfer of B1a lymphocytes into splenectomized mice increased peritoneal B1a lymphocytes; restored plasma IgM, oxidized low-density lipoprotein IgM levels, and lesion IgM deposits; and potently attenuated atherosclerotic lesions, with reduced lesion necrotic cores, oxidized low-density lipoprotein, and apoptotic cells. In contrast, transfer of B1a lymphocytes that cannot secrete IgM failed to protect against atherosclerosis development in splenectomized mice despite reconstitution in the peritoneum.

CONCLUSIONS:

B1a lymphocytes are an atheroprotective B-lymphocyte population. Our data suggest that natural IgM secreted by these lymphocytes offers protection by depositing IgM in atherosclerotic lesions, which reduces the necrotic cores of lesions.

• Authors: Tin Kyaw, Christopher Tay, Surendran Krishnamurthi, Peter Kanellakis, Alex Agrotis, Peter Tipping, Alex Bobik, Ban-Hock Toh
• Journal: Circulation research (Circ Res) Vol. 109 Issue 8 Pg. 830-40 (Sep 30 2011) ISSN: 1524-4571 [Electronic] United States
• PMID: 21868694 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin M
• secretory IgM

Topics

• Animals
• Atherosclerosis (immunology, pathology, prevention & control)
• B-Lymphocyte Subsets (immunology, metabolism, transplantation)
• Immunoglobulin M (biosynthesis, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Necrosis
• Splenectomy
• Tunica Intima (pathology)