CD154

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CD154 and T-dependent B cell activation[edit | edit source]

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Diagram of T-dependent B cell activation

CD154, also known as CD40 ligand, is a crucial protein involved in the immune system's response to antigens. It plays a significant role in T-dependent B cell activation, a process essential for the production of high-affinity antibodies and the establishment of immunological memory.

Structure and Expression[edit | edit source]

CD154 is a member of the tumor necrosis factor (TNF) superfamily and is primarily expressed on activated T cells. It is a type II transmembrane protein that interacts with CD40, a receptor found on B cells, dendritic cells, and other antigen-presenting cells.

Mechanism of Action[edit | edit source]

The interaction between CD154 and CD40 is pivotal for T-dependent B cell activation. When a helper T cell recognizes an antigen presented by a B cell, CD154 is upregulated on the T cell surface. This upregulation allows CD154 to bind to CD40 on the B cell, delivering a critical signal that promotes B cell proliferation, differentiation, and isotype switching.

Role in B Cell Activation[edit | edit source]

T-dependent B cell activation involves several steps:

1. Antigen Recognition: B cells recognize and internalize antigens through their B cell receptor (BCR). 2. Antigen Presentation: The internalized antigen is processed and presented on the B cell surface in association with MHC class II molecules. 3. T Cell Help: Helper T cells recognize the antigen-MHC complex and provide help through CD154-CD40 interaction. 4. B Cell Proliferation and Differentiation: The CD154-CD40 interaction, along with cytokines secreted by T cells, drives B cell proliferation and differentiation into plasma cells and memory B cells.

Clinical Significance[edit | edit source]

Defects in CD154 expression or function can lead to immunodeficiency disorders, such as Hyper-IgM syndrome, where patients have an impaired ability to produce certain types of antibodies. Conversely, overexpression of CD154 has been implicated in autoimmune diseases and chronic inflammation.

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Contributors: Prab R. Tumpati, MD