TY - JOUR AU - Tay, Christopher AU - Kanellakis, Peter AU - Hosseini, Hamid AU - Cao, Anh AU - Toh, Ban-Hock AU - Bobik, Alex AU - Kyaw, Tin PY - 2020 M3 - Original Research TI - B Cell and CD4 T Cell Interactions Promote Development of Atherosclerosis JO - Frontiers in Immunology UR - https://www.frontiersin.org/articles/10.3389/fimmu.2019.03046 VL - 10 SN - 1664-3224 N2 - 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. ER -