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• W2889311601 abstract "Co-ordinated interaction between distinct cell types is a hallmark of successful immune function. A striking example of this is the carefully orchestrated cooperation between helper T cells and B cells that occurs during the initiation and fine-tuning of T-cell dependent antibody responses. While these processes have evolved to permit rapid immune defense against infection, it is becoming increasingly clear that such interactions can also underpin the development of autoimmunity. Here we discuss a selection of cellular and molecular pathways that mediate T cell/B cell collaboration and highlight how in vivo models and genome wide association studies link them with autoimmune disease. In particular, we emphasize how CTLA-4-mediated regulation of CD28 signaling controls the engagement of secondary costimulatory pathways such as ICOS and OX40, and profoundly influences the capacity of T cells to provide B cell help. While our molecular understanding of the co-operation between T cells and B cells derives from analysis of secondary lymphoid tissues, emerging evidence suggests that subtly different rules may govern the interaction of T and B cells at ectopic sites during autoimmune inflammation. Accordingly, the phenotype of the T cells providing help at these sites includes notable distinctions, despite sharing core features with T cells imparting help in secondary lymphoid tissues. Finally, we highlight the interdependence of T cell and B cell responses and suggest that a significant beneficial impact of B cell depletion in autoimmune settings may be its detrimental effect on T cells engaged in molecular conversation with B cells." @default.
• W2889311601 created "2018-09-07" @default.
• W2889311601 creator A5008534430 @default.
• W2889311601 creator A5015262622 @default.
• W2889311601 creator A5016374387 @default.
• W2889311601 creator A5027364516 @default.
• W2889311601 creator A5053622449 @default.
• W2889311601 creator A5078878021 @default.
• W2889311601 creator A5081500106 @default.
• W2889311601 creator A5088584450 @default.
• W2889311601 date "2018-08-27" @default.
• W2889311601 modified "2023-10-17" @default.
• W2889311601 title "T Cell/B Cell Collaboration and Autoimmunity: An Intimate Relationship" @default.
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