Sandbox Reserved 1771: Difference between revisions

Many transmembrane interactions can be found within a IgM BCR. The <scene name='95/952699/Transmembrane_region/5'>α and β subunits</scene> have numerous interactions that keep them associated with each other. Residue interactions found within the α-β subunits, such as hydrogen bonds, ionic interactions, and hydrophobic interactions between nonpolar residues can be found <scene name='95/952699/Overview_hbonds_fixed/8'>here</scene>. At cellular pH, charged residues found in the transmembrane region strengthen the overall interaction through hydrogen bonds and ionic interactions. For example, <scene name='95/952699/N155_e138_hbonds_fixed/7'>a hydrogen bond</scene> between residues N155 and E138, along with numerous other hydrogen bonds, works to stabilize the α-β chain interactions in the transmembrane region. Further down the chains, <scene name='95/952699/T166_e148_hbonds_fixed/7'>hydrogen bonding</scene> between residues T166 and E148 work to keep the α-β subunit associated with each other. Overall, these hydrogen bonds and ion interactions work to maintain the association of the α-β chains, which allows the BCR to activate an immune response.

[[Image: FINAL1.PNG| 500 px|thumb | right| '''Figure 2.''' Diagram of B-cell formation, subsequent divergence, and attack of somatic cells seen in autoimmune diseases. All cell types are labeled and BCRs are shown in red, while antigens are shown in blue. When a defective BCR recognizes a somatic cell instead of a foreign pathogen, an immune response occurs, leading to degradation of tissue and disease.]]

The formation of B-cells occurs in the bone marrow from hematopoietic stem cells<ref name="Althwaiqeb">Althwaiqeb, S. ''Histology, B Cell Lymphocyte''; StatPearls Publishing, 2023. </ref>. Once formed, B-cell receptors are attached to B-cells through the aid of membrane-bound proteins in bone marrow cells. During this process, gene recombination occurs, which allows unique BCRs to become highly specific to different antigens<ref name="Althwaiqeb">Althwaiqeb, S. ''Histology, B Cell Lymphocyte''; StatPearls Publishing, 2023. </ref>. Once they are formed, [https://en.wikipedia.org/wiki/B_cell B-cells diverge] and become either memory cells or plasma cells <ref name="Wang Y">Wang Y, Liu J, Burrows PD, Wang JY. B Cell Development and Maturation. Adv Exp Med Biol. 2020;1254:1-22. doi: 10.1007/978-981-15-3532-1_1. PMID: 32323265.</ref>. Memory cells still have BCRs and initiate a faster immune response during a secondary infection, while plasma cells secrete antibodies for immediate response to foreign antigens <ref name="Althwaiqeb">Althwaiqeb, S. ''Histology, B Cell Lymphocyte''; StatPearls Publishing, 2023. </ref>.

B-cells and their respective receptors play an important role in the immune response. Misregulation can lead to damaging consequences. [https://en.wikipedia.org/wiki/Autoimmune_disease Autoimmune diseases] develop when somatic cells are recognized as foreign antigens and the body tries to eliminate them <Ref name="Yanaba K">Yanaba K, Bouaziz JD, Matsushita T, Magro CM, St Clair EW, Tedder TF. B-lymphocyte contributions to human autoimmune disease. Immunol Rev. 2008 Jun;223:284-99. doi: 10.1111/j.1600-065X.2008.00646.x. PMID: 18613843. </Ref> (figure 2). B-cell receptors are hypothesized to be an essential part of autoimmune disease development due to BCR function and role in the immune systems. In autoimmune diseases, BCRs improperly recognize somatic cells from different tissues and elicit the production of [https://en.wikipedia.org/wiki/Autoantibody autoantibodies]<Ref name="Yanaba K">Yanaba K, Bouaziz JD, Matsushita T, Magro CM, St Clair EW, Tedder TF. B-lymphocyte contributions to human autoimmune disease. Immunol Rev. 2008 Jun;223:284-99. doi: 10.1111/j.1600-065X.2008.00646.x. PMID: 18613843. </Ref>, causing the destruction of these cell types. Examples of these diseases include [https://en.wikipedia.org/wiki/Rheumatoid_arthritis rheumatoid arthritis] where the lining of joints is targeted and degraded, [https://en.wikipedia.org/wiki/Multiple_sclerosis multiple sclerosis] which targets the myelin sheath that surrounds nerve cells, [https://en.wikipedia.org/wiki/Type_1_diabetes type 1 diabetes mellitus] where the insulin producing cells are targeted for destruction, and [https://en.wikipedia.org/wiki/Lupus systematic lupus erythematosus] where multiple organ systems are targeted (skin, brain, lungs, and kidneys are common targets) <Ref name="Yanaba K">Yanaba K, Bouaziz JD, Matsushita T, Magro CM, St Clair EW, Tedder TF. B-lymphocyte contributions to human autoimmune disease. Immunol Rev. 2008 Jun;223:284-99. doi: 10.1111/j.1600-065X.2008.00646.x. PMID: 18613843. </Ref>.