China
Africa
Explore chapters and articles related to this topic
Analyzing Complex Polygenic Traits
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Bernard R. Lauwerys, Edward K. Wakeland
Recent work by Boackle et al identified the Cr2 gene, encoding complement receptors 1 and 2, as a positional candidate for Slelc. Comparisons of the NZM2410 and B6 alleles of Cr2 revealed several single nucleotide polymorphisms (SNP) that result in amino acid replacements in the sequence of the NZM2410 protein. One SNP introduces a novel glycosylation site in the C3d binding domain of the receptor, that reduces ligand-binding and receptor-mediated cell signaling. In addition to NZM2410 (and the parental NZW strain), two other strains share this polymorphic variant: NOD, which is a strain of diabetes-prone mice and SWR which is a parent for lupus prone SWF1 hybrids.75 Noteworthy, targeted disruption of the Cr2 gene in B6 mice (B6 Cr2-/-) has only limited effects on the production of autoantibodies. By contrast, mice that display a mutation of the Cr2 gene and concomitant mutation in Fas (B6/lpr Cr22-/-) produce significantly higher levels of anti-dsDNA antibodies than B6/lpr controls, thereby indicating that the Cr2 gene might be linked to the production of autoantibodies by modifying the effect of other lupus susceptibility genes.76
B Cells and Humoral Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
We have seen that there are several pathways by which resting B cells may be induced to begin cycling. B cells may be activated by binding of type 1 antigens (mitogens) to mitogen receptors, by binding of type 2 antigens to Ig receptors and/or to mitogen receptors followed by Th cell-derived activating factors, and by appropriate MHC-determined contacts with activated Th cells. In addition, B cells may receive an activating signal through Fc receptors, complement receptors (e.g., the C3d/EBV receptor CR2, or CD21), class II histocompatibility molecules, or by cross-linking surface Ig with anti-Ig antibodies. In most cases, T cell-derived signals are required to initiate proliferation and differentiation. The precise manner in which all of these different situations activate B cells is not yet known.
The complement system in health and disease
Published in Gabriel Virella, Medical Immunology, 2019
Activation of the complement system by whichever pathway leads to the generation of proteolytic cleavage fragments that have distinct biological functions. In a way, each step of the complement activation pathway is designed to elicit the help and support of other immune mediators to deal with the infectious agent. While the complement system is thought to be a key effector system of innate immunity, the generation of many of the complement fragments enables it to bridge, prime, and activate mechanisms of the adaptive immune response (Table 9.4). The cleavage fragments interact with high-affinity complement receptors present on the surface of innate and adaptive immune cells and are further present on parenchymal cells to promote processes such as vascular permeability and vasoconstriction. There are five distinct receptors that have been described to interact with different fragments of C3. Complement receptor type 1 (CR1, CD35) is a widely distributed molecule found on erythrocytes, neutrophils, mononuclear phagocytes, B cells, and some T cells. CR1 binds to both C4b and C3b ligands, which are the initial degradation products of C4 and C3 that are covalently bound to the membrane surface. Engagement of CR1 leads to a variety of functional outcomes dependent largely on the cell type on which it is expressed. For example, CR1 present on erythrocytes is important for processing immune complexes, whereas expression on neutrophils and macrophages acts to promote phagocytosis. On B lymphocytes, CR1 serves as a processing molecule to convert C3b to iC3b, and as a competitive receptor to complement receptor 2 (CR2) to downregulate responses to C3b-coated antigen.
Autoimmune disorders associated with common variable immunodeficiency: prediction, diagnosis, and treatment
Published in Expert Review of Clinical Immunology, 2022
Niloufar Yazdanpanah, Nima Rezaei
Complement receptor type 2 (CR2, also known as CD21) is expressed on different immune cells. On B cells, CD21 contributes to the formation of a complex with CD19 and CD81. The complex acts as a coreceptor for the B cell receptor (BCR), which decreases the threshold of B cell activation upon stimulation [43,44]. B cells express CD21 based on their maturation stage; circulating naïve B cells and memory B cells express higher levels of CD21 compared to plasma cells [45]. A genetic defect of CD21 is associated with hypogammaglobulinemia [46]. Current data underpins that CD21low B cells derive from either memory B cells or plasma cells following chronic stimulation with extrinsic antigens [47]. CD21low B cells have shown weak proliferation through BCR signaling and demonstrated a shorter half-life compared with CD21+ B cells. Furthermore, despite representing an activated phenotype, CD21low B cells express inhibitory receptors. On the other hand, expansion of CD21low B cells was reported in autoreactive clones of immune cells [48–50]. Rakhmanov et al. described CD21low B cells as pre-activated polyclonal cells, which represent an attenuated function and are mainly localized in peripheral tissues [51]. Following provocation via CD40L, IL-2, and IL-10, CD21low B cells release higher levels of IgM in comparison with naïve B cells; high IgM level is proposed to be linked with the development of autoimmune conditions in CVID patients [14,52,53].
CARMIL2 Immunodeficiency with Epstein Barr Virus Associated Smooth Muscle Tumor (EBV-SMT). Report of a Case with Comprehensive Review of Literature
Published in Fetal and Pediatric Pathology, 2022
Mukul Vij, Meena Sivasankaran, Dhaarani Jayaraman, Srinivas Sankaranarayanan, Vimal Kumar, Deenadayalan Munirathnam, Julius Scott
Pathogenetic mechanism of EBV-SMT is still debated but it has been suggested to be related with an uncontrolled proliferation of EBV-infected lymphocytes which fuses with smooth muscle cells and induce neoplastic transformation [30]. EBV-SMT in patients with HIV have been shown to express complement receptor 2 (CR2 or CD21), indicating that EBV-infected lymphocytes play a role in pathogenesis [31]. Normal smooth muscle cells express the CD21 receptor and can be directly infected with EBV. Facilitating and promoting replication within these cells has also been proposed as another pathomechanism [32]. A majority of solid organ and bone marrow transplant-associated EBV-SMT and all analyzed cases of EBV-SMT in patients with PID are negative for CD21 indicating undiscovered pathways in tumorigenesis [29]. It has also been postulated that immunosuppression may play a role in allowing abnormal EBV cellular entry. EBV-SMT has been shown to demonstrate EBV type III latency pattern, i.e., cells are positive for EBV nuclear antigen 2 (EBNA2), EBNA3, and LMP1. Ong et al investigated molecular pathways in post organ transplant EBV-SMT and suggested activation of the mTOR/Akt pathway [33]. This activation has been shown to be triggered by EBV protein LMP2A suggesting critical role of EBV in tumorigenesis [33]. Methylation of RASSF1A and promoter hypermethylation of RARβ, GSTP1, DAPK, and p14 were also observed [33]. Increased expression of proto-oncogene MYC and microRNA expression profile which is related to smooth muscle differentiation but not EBV infection has also been also reported in post-transplant EBV-SMT [32, 34].
Complement system network in cell physiology and in human diseases
Published in International Reviews of Immunology, 2021
Roberta Romano, Giuliana Giardino, Emilia Cirillo, Rosaria Prencipe, Claudio Pignata
Four receptors are part of the complement system. Complement Receptor 1 is expressed on macrophages and red blood cells whose role is to promote the clearance of immune-complexes; Complement Receptor 2 is expressed on B cells where, upon binding of the fragment C3d opsonizing antigens, it enhances B cell receptor signaling. Complement Receptor 3 and Complement Receptor 4, belonging to beta-2 (CD18) integrin family [14], are expressed on monocytes, dendritic cells and macrophages and take part to opsonization and phagocytic process.