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The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
B-cell specificity is conferred by the B-cell receptor (BCR) (Figure 2.12), which can be expressed as a membrane-bound receptor or in a soluble form as an antibody (Ab) or immunoglobulin (Ig). The human immune system can produce a highly diverse repertoire of B-cell receptors and antibodies through combinatorial rearrangements of multiple gene segments and somatic mutation. Each antibody clone can bind a specific target epitope, exerting immune functions by blocking or neutralising the target antigen, or flagging it for destruction by other immune cells.
The Inducible Defense System: The Induction and Development of the Inducible Defence
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Michael A. Hickey, Diane Wallace Taylor
Each B and T cell expresses an antigen-specific receptor on its surface that allows it to interact with a single epitope on an antigen. The receptor on B cells is called the B cell receptor (BcR). This receptor, which was discussed in the previous chapter, is made up of a membrane-bound antibody molecule which is associated with two transmembrane proteins, Igα and Igβ (Figure 8.2). The B cell receptor directly binds to epitopes expressed on antigens that can be made up of proteins, carbohydrates, lipids, as well as many organic compounds.
Inflammation and immunology
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Christopher Bellamy, Stephen J. Jenkins, Henry J. McSorley, David A. Dorward, Timothy J. Kendall
B lymphocytes become activated and proliferate when antigen binds to and cross-links the B-cell receptor molecules on the surface. The B-cell receptor is composed of monomeric IgM (see below) existing in a transmembrane form with the antigen-binding fragment (Fab) at the external surface and the Fc fragment at the cytoplasmic face. The crosslinking of the B-cell receptor provides one signal for B-cell activation but, for complete activation, a second signal termed co-stimulation is needed. This is usually provided by B-cell CD40 co-stimulated by a CD40 ligand (CD154) on a helper T cell and is particularly important for activated B cells to switch the type of immunoglobulin isoforms they make. Activated B cells subsequently differentiate into plasma cells that synthesize and secrete large quantities of immunoglobulin into the plasma.
Nanomaterials in tuberculosis DNA vaccine delivery: historical perspective and current landscape
Published in Drug Delivery, 2022
Xing Luo, Xiaoqiang Zeng, Li Gong, Yan Ye, Cun Sun, Ting Chen, Zelong Zhang, Yikun Tao, Hao Zeng, Quanming Zou, Yun Yang, Jieping Li, Hongwu Sun
The delivery of protein expressed as an adjuvant molecule with plasmid DNA causes enhanced protective efficacy against a challenge infection with M. tuberculosis H37Rv, emphasizing the significant role of CD4+ helper T cells (Th1-type) in protection (Tanghe et al., 2001, Yang et al., 2011). Figure 7 shows self-assembled protein nanoparticles in vaccine design. B- and T-cell stimulation and activation, and the subsequent secretion of antigen-specific antibodies by plasma cells depend on the effective cross-linking between B-cell surface immunoglobulins (B-cell receptors, BCRs) and recognition patterns presented by the pathogen. The high-density and structurally ordered antigenic array presented by nanoparticle vaccines facilitate multiple binding events to occur simultaneously between the self-assembling protein nanoparticles and host-cell BCRs (Lopez-Sagaseta et al., 2016). Several paradigms have been reported for the design of TB DNA-vaccine delivery vectors using protein-backbone engineering. The synthetic antimicrobial peptide KLKL5KLK exhibits effective immunostimulant properties that enhance and prolong immune responses against M. tuberculosis in combination with DNA vaccines (Li et al., 2008). Therefore, these self-assembled peptide and protein nanomaterials represent novel TB DNA-vaccine delivery systems with immense application prospects.
Current advances in biopharmaceutical informatics: guidelines, impact and challenges in the computational developability assessment of antibody therapeutics
Published in mAbs, 2022
Rahul Khetan, Robin Curtis, Charlotte M. Deane, Johannes Thorling Hadsund, Uddipan Kar, Konrad Krawczyk, Daisuke Kuroda, Sarah A. Robinson, Pietro Sormanni, Kouhei Tsumoto, Jim Warwicker, Andrew C.R. Martin
Immune responses to disease, and also therapies, can be profiled using BCR repertoires to investigate B cell subtype involvement and levels of antibody response. Using such analysis, we can distinguish between healthy and disease repertoires and learn about disease mechanisms, particularly those associated with B cells, such as autoimmune diseases, chronic lymphoid leukemia, and other cancers.154,155 In the future, such information will hopefully be used to improve patient outcomes by identifying the most at-risk patients, tracking disease progression and monitoring response to therapies. A better understanding of the immune system involvement in disease may also indicate targets for potential therapeutic intervention, and even suggest antibody drug candidates present in the BCR repertoires of patients with the disease.
Paediatric-type follicular lymphoma arising in conjunction with pregnancy
Published in Acta Oncologica, 2021
Stefano Fratoni, Pasquale Niscola
The case of PTNFL was observed by us in a young female. This particularly rare lymphoma typically presents with isolated lymphadenopathy in the head and neck. Despite the ‘blastoid’ features on histological examination, PTNFL has an extremely indolent clinical behaviour, being surgical excision alone virtually curative [5–6]. Nonetheless, exceptional cases of transformation in high-grade B-cell lymphoma may occur [7]. The differential diagnosis of PTNFL may be quite troublesome. The recognition of this particularly rare lymphoma is important for hematopathologist, given that overlap with florid reactive follicular hyperplasia (RFH) may be a practical problem. Reliable criteria for its diagnosis have been previously illustrated [8]. In this setting the immunohistochemical expression of forehead box protein P1 FOXP-1 may be a useful tool to distinguish PTNFL from RFH [9]. Nonetheless, establish clonality by B-cell receptor studies is mandatory in the diagnostic work up. On the other hand, purely follicular large B-cell lymphoma with IRF4 rearrangement may mimic PTNFL. The strong nuclear expression of IRF4/MUM1 along with rearrangement of IRF4 with an IGH locus, usually allows the distinction between the two [10].