Sandbox Reserved 1771: Difference between revisions

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==Introduction==

B-cells play an important role of the human immune system ~~and can be found circulating throughout the body~~. On the surface of B-cells, membrane bound [https://en.wikipedia.org/wiki/B-cell_receptor B-cell receptors](BCRs) ~~can be found~~ <Ref name="Robinson R">Robinson R. Distinct B cell receptor functions are determined by phosphorylation. PLoS Biol. 2006 Jul;4(7):e231. doi: 10.1371/journal.pbio.0040231. Epub 2006 May 30. PMID: 20076604; PMCID: PMC1470464.</Ref>. ~~These complex proteins are made up of membrane bound immunoglobulins (mIg). There are several~~ different types of BCRs~~, namely~~ [https://en.wikipedia.org/wiki/Immunoglobulin_G IgG], [https://en.wikipedia.org/wiki/Immunoglobulin_A IgA], [https://en.wikipedia.org/wiki/Immunoglobulin_M IgM], [https://en.wikipedia.org/wiki/Immunoglobulin_E IgE], or [https://en.wikipedia.org/wiki/Immunoglobulin_D IgD]~~. Each specific BCR has important~~ functions for different diseases~~, but~~ the ~~IgM BCR in particular is most interesting~~. ~~The BCR consists mainly~~ of three domains: extracellular, transmembrane, and intracellular. ~~While the~~ extracellular region makes up most of the protein, ~~perhaps~~ the ~~most interesting~~ interactions ~~can be found in the transmembrane domain~~. Unlike other BCRs, the IgM BCR has a specific heavy chain interaction with the α-β subunit of the protein<Ref name="Su Q"> Su Q, Chen M, Shi Y, Zhang X, Huang G, Huang B, Liu D, Liu Z, Shi Y. Cryo-EM structure of the human IgM B cell receptor. Science. 2022 Aug 19;377(6608):875-880. [doi: 10.1126/science.abo3923. Epub 2022 Aug 18. PMID: 35981043.]</Ref>. The role of BCRs is to bind to foreign antigens and initiate the appropriate immune response. Once bound to an antigen, the ~~IgM~~ BCR undergoes a conformational change in the extracellular region~~. While the exact conformational change is still not known, preliminary studies suggest that there is separation of Fab fragments that opens the binding site within the BCR~~. This initiates several signal transduction pathways, which are responsible for processing the antigen and initiating the appropriate immune responses. ~~More specifically~~, the α-β subunit ~~is connected to the phosphorylation of an~~ [https://en.wikipedia.org/wiki/Immunoreceptor_tyrosine-based_activation_motif immunoreceptor tyrosine-based activation motif]~~(ITAM)~~ upon binding. This in turn triggers the activation of kinases downstream that aid in the immune response.

B-cells play an important role in the human immune system by creating specific antibodies against foreign pathogens. On the surface of B-cells, membrane bound [https://en.wikipedia.org/wiki/B-cell_receptor B-cell receptors](BCRs) play a role in recognizing antigens. <Ref name="Robinson R">Robinson R. Distinct B cell receptor functions are determined by phosphorylation. PLoS Biol. 2006 Jul;4(7):e231. doi: 10.1371/journal.pbio.0040231. Epub 2006 May 30. PMID: 20076604; PMCID: PMC1470464.</Ref>. Several different types of BCRs( [https://en.wikipedia.org/wiki/Immunoglobulin_G IgG], [https://en.wikipedia.org/wiki/Immunoglobulin_A IgA], [https://en.wikipedia.org/wiki/Immunoglobulin_M IgM], [https://en.wikipedia.org/wiki/Immunoglobulin_E IgE], or [https://en.wikipedia.org/wiki/Immunoglobulin_D IgD]) perform distinct functions for different diseases by activating different pathways depending on the antigen. BCRs consist of three domains: extracellular, transmembrane, and intracellular. The extracellular region makes up most of the protein, which is where antigen binding occurs. The focus of this page will be the IgM BCR and its unique interactions. Unlike other BCRs, the IgM BCR has a specific heavy chain interaction with the α-β subunit (part of the transmembrane region) of the protein<Ref name="Su Q"> Su Q, Chen M, Shi Y, Zhang X, Huang G, Huang B, Liu D, Liu Z, Shi Y. Cryo-EM structure of the human IgM B cell receptor. Science. 2022 Aug 19;377(6608):875-880. [doi: 10.1126/science.abo3923. Epub 2022 Aug 18. PMID: 35981043.]</Ref>. The role of BCRs is to bind to foreign antigens and initiate the appropriate immune response. Once bound to an antigen, the BCR undergoes a conformational change in the extracellular region. This initiates several signal transduction pathways, which are responsible for processing the antigen and initiating the appropriate immune responses. To initiate the intracellular signal, the α-β subunit activates a tyrosine kinase motif [https://en.wikipedia.org/wiki/Immunoreceptor_tyrosine-based_activation_motif immunoreceptor tyrosine-based activation motif] upon binding of an antigen. This in turn triggers the activation of kinases downstream that aid in the immune response. This page will cover the structure, intermolecular interactions, formation of B-cells, and therapeutic uses for B-cells in more detail.

==Structure==

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 <StructureSection load='4INS' size='350' side='right' caption='Human mIgM B Cell Receptor. Heavy chain 1 is represented in blue, heavy chain 2 in magenta, light chain 1 in green, and light chain 2 in yellow. Iga is shown in red while Igb is in orange. [https://www.rcsb.org/structure/7XQ8 7XQ8]' scene='95/952699/Overview_spin/1'>
 ==Introduction==
-B-cells play an important role of the human immune system and can be found circulating throughout the body. On the surface of B-cells, membrane bound [https://en.wikipedia.org/wiki/B-cell_receptor B-cell receptors](BCRs) can be found <Ref name="Robinson R">Robinson R. Distinct B cell receptor functions are determined by phosphorylation. PLoS Biol. 2006 Jul;4(7):e231. doi: 10.1371/journal.pbio.0040231. Epub 2006 May 30. PMID: 20076604; PMCID: PMC1470464.</Ref>. These complex proteins are made up of membrane bound immunoglobulins (mIg).  There are several different types of BCRs, namely [https://en.wikipedia.org/wiki/Immunoglobulin_G IgG], [https://en.wikipedia.org/wiki/Immunoglobulin_A IgA], [https://en.wikipedia.org/wiki/Immunoglobulin_M IgM], [https://en.wikipedia.org/wiki/Immunoglobulin_E IgE], or [https://en.wikipedia.org/wiki/Immunoglobulin_D IgD]. Each specific BCR has important functions for different diseases, but the IgM BCR in particular is most interesting. The BCR consists mainly of three domains: extracellular, transmembrane, and intracellular. While the extracellular region makes up most of the protein, perhaps the most interesting interactions can be found in the transmembrane domain. Unlike other BCRs, the IgM BCR has a specific heavy chain interaction with the α-β subunit of the protein<Ref name="Su Q"> Su Q, Chen M, Shi Y, Zhang X, Huang G, Huang B, Liu D, Liu Z, Shi Y. Cryo-EM structure of the human IgM B cell receptor. Science. 2022 Aug 19;377(6608):875-880. [doi: 10.1126/science.abo3923. Epub 2022 Aug 18. PMID: 35981043.]</Ref>. The role of BCRs is to bind to foreign antigens and initiate the appropriate immune response. Once bound to an antigen, the IgM BCR undergoes a conformational change in the extracellular region. While the exact conformational change is still not known, preliminary studies suggest that there is separation of Fab fragments that opens the binding site within the BCR. This initiates several signal transduction pathways, which are responsible for processing the antigen and initiating the appropriate immune responses. More specifically, the α-β subunit is connected to the phosphorylation of an [https://en.wikipedia.org/wiki/Immunoreceptor_tyrosine-based_activation_motif immunoreceptor tyrosine-based activation motif](ITAM) upon binding. This in turn triggers the activation of kinases downstream that aid in the immune response.
+B-cells play an important role in the human immune system by creating specific antibodies against foreign pathogens. On the surface of B-cells, membrane bound [https://en.wikipedia.org/wiki/B-cell_receptor B-cell receptors](BCRs) play a role in recognizing antigens. <Ref name="Robinson R">Robinson R. Distinct B cell receptor functions are determined by phosphorylation. PLoS Biol. 2006 Jul;4(7):e231. doi: 10.1371/journal.pbio.0040231. Epub 2006 May 30. PMID: 20076604; PMCID: PMC1470464.</Ref>. Several different types of BCRs( [https://en.wikipedia.org/wiki/Immunoglobulin_G IgG], [https://en.wikipedia.org/wiki/Immunoglobulin_A IgA], [https://en.wikipedia.org/wiki/Immunoglobulin_M IgM], [https://en.wikipedia.org/wiki/Immunoglobulin_E IgE], or [https://en.wikipedia.org/wiki/Immunoglobulin_D IgD]) perform distinct functions for different diseases by activating different pathways depending on the antigen. BCRs consist of three domains: extracellular, transmembrane, and intracellular. The extracellular region makes up most of the protein, which is where antigen binding occurs. The focus of this page will be the IgM BCR and its unique interactions. Unlike other BCRs, the IgM BCR has a specific heavy chain interaction with the α-β subunit (part of the transmembrane region) of the protein<Ref name="Su Q"> Su Q, Chen M, Shi Y, Zhang X, Huang G, Huang B, Liu D, Liu Z, Shi Y. Cryo-EM structure of the human IgM B cell receptor. Science. 2022 Aug 19;377(6608):875-880. [doi: 10.1126/science.abo3923. Epub 2022 Aug 18. PMID: 35981043.]</Ref>. The role of BCRs is to bind to foreign antigens and initiate the appropriate immune response. Once bound to an antigen, the BCR undergoes a conformational change in the extracellular region. This initiates several signal transduction pathways, which are responsible for processing the antigen and initiating the appropriate immune responses. To initiate the intracellular signal, the α-β subunit activates a tyrosine kinase motif [https://en.wikipedia.org/wiki/Immunoreceptor_tyrosine-based_activation_motif immunoreceptor tyrosine-based activation motif] upon binding of an antigen. This in turn triggers the activation of kinases downstream that aid in the immune response. This page will cover the structure, intermolecular interactions, formation of B-cells, and therapeutic uses for B-cells in more detail.
 ==Structure==