6.2 B cell receptor structure and signaling
2 min read•july 25, 2024
B cell receptors are crucial for immune response. They consist of membrane-bound immunoglobulins and signaling components that recognize antigens and trigger activation. Understanding their structure and function is key to grasping how B cells defend against pathogens.
When B cell receptors bind antigens, they kick off complex signaling cascades. These involve kinase activation, second messenger generation, and transcription factor activation. Co-receptors fine-tune the response, either enhancing or dampening signaling to control B cell activation.
B Cell Receptor Structure
Structure of B cell receptor complex
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- (mIg) consists of two heavy chains and two light chains forming antigen-binding sites in variable regions
- Signaling components include (CD79a) and (CD79b) heterodimer with cytoplasmic tails containing ITAM motifs crucial for
- Accessory molecules CD19, CD21 (complement receptor 2), and CD81 enhance BCR signaling and lower activation threshold
B cell receptor in antigen recognition
- Variable regions of mIg bind specific epitopes enabling of B cells with matching receptors
- Antigen binding triggers conformational changes initiating intracellular signaling cascades
- Receptor-mediated endocytosis internalizes bound antigens for processing and presentation on MHC class II molecules
B Cell Receptor Signaling
Signaling cascades of B cell activation
- Tyrosine kinase activation: Lyn kinase phosphorylates ITAM motifs, recruiting and activating Syk kinase
- Signaling complex formation: BLNK (SLP-65) acts as scaffold protein recruiting Btk and PLCγ2
- Second messenger generation: PLCγ2 cleaves PIP2 into IP3 and DAG, IP3 triggers calcium release from endoplasmic reticulum
- Transcription factor activation: pathway activated by , activated through calcium-calcineurin pathway, pathway activated
- Cellular responses: Proliferation, differentiation, cytokine production, and antibody class switching initiated
Co-receptors in B cell signaling
- CD19-CD21-CD81 complex lowers activation threshold and enhances BCR signaling through PI3K pathway
- CD45 dephosphorylates inhibitory tyrosine residues on Src-family kinases promoting BCR signaling initiation
- CD22 negatively regulates BCR signaling by recruiting SHP-1 phosphatase to dampen activation
- FcγRIIB inhibits signaling by recruiting SHIP phosphatase to counteract PI3K signaling
- CD40 provides co-stimulatory signals enhancing B cell survival, proliferation, and isotype switching upon binding CD40L
- Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns synergizing with BCR signaling to enhance B cell activation
Key Terms to Review (17)
Cd79: CD79 is a protein that plays a crucial role as an integral part of the B cell receptor (BCR) complex, which is essential for B cell development and activation. It forms a heterodimer with immunoglobulin (Ig) and associates with signaling molecules to initiate intracellular signaling pathways upon antigen binding, influencing B cell proliferation, differentiation, and antibody production.
Clonal Selection: Clonal selection is the process by which specific B and T lymphocytes are activated and proliferate in response to an antigen, leading to the production of a clonal population of cells that can effectively target that antigen. This mechanism is crucial for generating the diversity of antibodies and T cell receptors needed for adaptive immunity, as well as ensuring that only those lymphocytes that can recognize a specific pathogen are expanded.
Epitope: An epitope is a specific part of an antigen that is recognized by the immune system, particularly by antibodies, B cells, and T cells. It plays a crucial role in the immune response as it is the precise site where these immune components bind, initiating a cascade of protective actions. Epitopes can be linear, consisting of a continuous sequence of amino acids, or conformational, formed by the three-dimensional structure of the antigen.
Erk/mapk: ERK/MAPK refers to a signaling pathway known as Extracellular Signal-Regulated Kinase/ Mitogen-Activated Protein Kinase, which plays a crucial role in cellular processes such as growth, differentiation, and survival. This pathway is activated by various receptors, including the B cell receptor, and transmits signals from the cell surface to the nucleus, influencing gene expression and cellular responses.
Igα: igα is an essential signaling component associated with the B cell receptor (BCR) that plays a crucial role in B cell activation and development. It functions as an adaptor protein that helps transduce signals from the BCR upon antigen binding, enabling the initiation of intracellular signaling cascades that lead to B cell proliferation, differentiation, and antibody production.
Igβ: igβ, or immunoglobulin beta, is a critical component of the B cell receptor (BCR) complex that plays a vital role in B cell signaling. It functions alongside immunoglobulin alpha (igα) to facilitate signal transduction upon antigen binding to the BCR, ultimately influencing B cell activation, proliferation, and differentiation into antibody-secreting plasma cells. The structure and signaling capacity of igβ are essential for the immune response.
IL-21: Interleukin-21 (IL-21) is a cytokine that plays a crucial role in the immune response, particularly in the regulation of B cell activation, differentiation, and proliferation. It is produced mainly by CD4+ T cells and has significant effects on the function of B cells by enhancing their ability to produce antibodies and promoting class switching. Understanding IL-21 is important for grasping how B cell receptor signaling can be influenced in adaptive immunity.
IL-4: IL-4, or Interleukin-4, is a cytokine produced primarily by T helper 2 (Th2) cells that plays a crucial role in the immune system by promoting B cell differentiation, enhancing antibody production, and influencing T cell activation and differentiation. This cytokine is essential for the development of Th2 responses and supports various immune functions, particularly in allergic responses and protection against parasitic infections.
Membrane-bound immunoglobulin: Membrane-bound immunoglobulin refers to the form of immunoglobulin that is expressed on the surface of B cells, acting as a B cell receptor (BCR). This form is essential for B cell activation, as it allows B cells to recognize and bind to specific antigens, leading to signal transduction that promotes B cell proliferation and differentiation into plasma cells.
Memory B cells: Memory B cells are long-lived immune cells that arise after an initial infection or vaccination, enabling a faster and stronger antibody response upon re-exposure to the same pathogen. These specialized cells are crucial for adaptive immunity, as they provide lasting protection and immunological memory.
Nf-κb: NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) is a transcription factor that plays a crucial role in regulating immune response, cell proliferation, and survival. It is found in the cytoplasm of cells in an inactive form bound to an inhibitor, and upon various stimuli, it gets activated, translocates to the nucleus, and initiates the expression of target genes involved in inflammation, immunity, and cell survival, making it pivotal in B cell receptor signaling.
NFAT: NFAT, or Nuclear Factor of Activated T-cells, is a family of transcription factors that play a crucial role in the immune response by regulating gene expression in response to calcium signals. These proteins are key players in T-cell activation and differentiation, and they also influence B-cell functions when signaling through the B cell receptor (BCR). By translocating to the nucleus upon stimulation, NFAT helps orchestrate the immune response by activating genes necessary for T-cell and B-cell development and function.
PKC: Protein Kinase C (PKC) is a family of protein kinase enzymes that play a vital role in various cellular signaling pathways, particularly those related to the immune response. PKC is activated by the presence of diacylglycerol (DAG) and calcium ions, and it modulates several physiological processes, including cell proliferation, differentiation, and apoptosis. This makes it especially important in the context of B cell receptor signaling, as it helps transmit signals that influence B cell activation and function.
Plasma Cells: Plasma cells are specialized B cells that produce large quantities of antibodies, playing a crucial role in the immune response. They are formed from activated B cells following exposure to antigens, and their primary function is to secrete antibodies that target specific pathogens, helping to neutralize infections and promote clearance.
Primary response: The primary response is the initial immune reaction that occurs when the body first encounters a specific antigen. During this response, naive B cells are activated, leading to the production of antibodies and the formation of memory cells. This process is crucial for establishing a long-term defense against pathogens and lays the foundation for subsequent immune responses.
Secondary response: The secondary response refers to the adaptive immune system's heightened and more efficient reaction upon re-exposure to a specific antigen, primarily mediated by memory cells that were generated during the primary immune response. This response is characterized by a quicker production of antibodies and a more robust activation of immune cells, enhancing the body's ability to eliminate pathogens more effectively than during the initial encounter.
Signal Transduction: Signal transduction is the process by which a cell converts an external signal into a functional response, often involving a series of molecular events. This complex communication system allows cells to respond to various stimuli, including hormones, cytokines, and antigens, leading to cellular changes such as movement, activation, or differentiation. It plays a crucial role in various physiological processes, including immune responses, where it facilitates leukocyte trafficking, T cell activation, and B cell receptor signaling.