B Cell and CD4 T Cell Interactions Promote Development of Atherosclerosis.

Abstract

Interaction between B and CD4 T cells is crucial for their optimal responses in adaptive immunity. Immune responses augmented by their partnership promote chronic inflammation. Here we report that interaction between B and CD4 T cells augments their atherogenicity to promote lipid-induced atherosclerosis. Genetic deletion of the gene encoding immunoglobulin mu (μ) heavy chain (μMT) in ApoE-/- mice resulted in global loss of B cells including those in atherosclerotic plaques, undetectable immunoglobulins and impaired germinal center formation. Despite unaffected numbers in the circulation and peripheral lymph nodes, CD4 T cells were also reduced in spleens as were activated and memory CD4 T cells. In hyperlipidemic μMT-/- ApoE-/- mice, B cell deficiency decreased atherosclerotic lesions, accompanied by absence of immunoglobulins and reduced CD4 T cell accumulation in lesions. Adoptive transfer of B cells deficient in either MHCII or co-stimulatory molecule CD40, molecules required for B and CD4 T cell interaction, into B cell-deficient μMT-/- ApoE-/- mice failed to increase atherosclerosis. In contrast, wildtype B cells transferred into μMT-/- ApoE-/- mice increased atherosclerosis and increased CD4 T cells in lesions including activated and memory CD4 T cells. Transferred B cells also increased their expression of atherogenic cytokines IL-1β, TGF-β, MCP-1, M-CSF, and MIF, with partial restoration of germinal centers and plasma immunoglobulins. Our study demonstrates that interaction between B and CD4 T cells utilizing MHCII and CD40 is essential to augment their function to increase atherosclerosis in hyperlipidemic mice. These findings suggest that targeting B cell and CD4 T cell interaction may be a therapeutic strategy to limit atherosclerosis progression.

• Authors: Christopher Tay, Peter Kanellakis, Hamid Hosseini, Anh Cao, Ban-Hock Toh, Alex Bobik, Tin Kyaw
• Journal: Frontiers in immunology (Front Immunol) Vol. 10 Pg. 3046 ( 2019) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 31998318 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Tay, Kanellakis, Hosseini, Cao, Toh, Bobik and Kyaw.

Chemical References

• Apolipoproteins E
• Cytokines
• Immunoglobulins

Topics

• Animals
• Apolipoproteins E (immunology)
• Atherosclerosis (immunology)
• B-Lymphocytes (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Cytokines (immunology)
• Immunoglobulins (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Plaque, Atherosclerotic (immunology)