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Sjögren's Disease
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
B and T cells infiltrating the salivary glands of SjD can organize into so-called ectopic lymphoid structures (ELS), with germinal centers and surrounding mantle and marginal zones of lymphocytes, as is seen in secondary lymphoid organs. These ELS exhibit functional features of germinal centers with antigen presentation and antibody production (135). B cells and plasma cells associated with ELS frequently display autoreactivity toward disease-specific autoantigens, actively contributing to the maintenance of autoimmunity (136). ELS form around intercalated ducts, underscoring the central role of ductal epithelial cells as an active player in the initiation and perpetuation of autoimmunity in SjD (autoimmune epithelitis) (137). ELS are present in about 30–40% of SjD patients with a focus score of ≥1 (138–143) and are associated with more severe systemic manifestations, including higher frequencies of autoantibodies and higher disease severity (144–146). A higher risk of B cell lymphoma was observed in some reports (142, 147), but not in others (148–150). A major issue in identifying ELS is the lack of a standardized detection method in tissue samples. Immunohistochemical staining for CD21 and BCL6 is used most commonly (148, 151).
Comparative Immunology
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Although birds are commonly considered not to possess lymph nodes, they do possess structures that can be considered to be their functional equivalent. These avian lymph nodes consist of a central sinus that is the main lumen of a lymphatic vessel. It is surrounded by a sheath of lymphoid tissue that contains germinal centers. Avian lymph nodes have no external capsule.
Inherited Defects in Immune Defenses Leading to Pulmonary Disease
Published in Stephen D. Litwin, Genetic Determinants of Pulmonary Disease, 2020
Lymphatic tissue fails to show germinal centers; plasma cells are missing from the bone marrow, intestinal tract, and lymph nodes. Circulating blood lymphocytes do not include Β lymphocytes with surface Ig. Τ lymphocytes are quantitatively and functionally normal.
Immune-based therapies in diffuse large B-cell lymphoma
Published in Expert Opinion on Investigational Drugs, 2023
Dustin McCurry, Christopher R. Flowers, Casey Bermack
Diffuse large B-cell lymphoma (DLBCL) is an aggressive and clinically heterogeneous malignancy with up to 40% of patients experiencing primary refractory disease or relapse after first-line treatment [1]. DLBCL originates from B-cells developing through humoral immune responses. Upon initial germinal center (GC) formation, B-cells undergo somatic hypermutation and proliferation in GC dark zones prior to selection and activation in GC light zones, potentially repeating this cycle between GC dark and light zones for affinity maturation of B-cell receptors. Upon sufficient maturation, activated B-cells leave GCs and may develop into memory B-cells or terminally differentiate into plasma cells [2]. In the early 2000s, transcriptomic analyses subdivided DLBCL into at least two biologic classes, a group of tumors that are transcriptionally similar to germinal center B-cells (GCB) and another with similarities to activated B-cells (ABC), which confers poor prognosis [2,3].
Tertiary Lymphoid Structures, Immune Response, and Prognostic Relevance in Non-Small Cell Lung Cancer
Published in Cancer Investigation, 2023
Alexandra Giatromanolaki, Paschalis Chatzipantelis, Constantinos A. Contrafouris, Michael I. Koukourakis
The density of TLS was assessed in the tumor periphery and the inner tumor area, in hematoxylin–eosin tissue sections, in all available optical fields. As ‘tumor periphery’ was defined the area comprised by the first ×200 optical field containing tumor invading front and normal lung adjacent to this front. TLSs were identified in the stroma of the invading tumor and in the normal lung infiltrated by the tumor. Inner tumor areas refer to all available ×200 optical fields of the tumoral tissue section, immediately below the optical filed that defined the tumor periphery. TLSs were identified in the stroma areas. Necrotic areas were excluded. All tertiary lymphoid structures with or without identifiable germinal centers were recorded. The whole tissue section was analyzed at ×200 magnification power. The number of TLS in normal lung across the tumor periphery was recorded and divided by the number of optical fields to provide the peritumoral ‘pTLS-score’. A similar procedure was applied within the tumor body, where after counting the TLS number in all ×200 optical fields, we produced the inner tumor area ‘iTLS-score’, by dividing the total TLS number with the number of optical fields.
Transcriptional regulation of B cell class-switch recombination: the role in development of noninfectious complications
Published in Expert Review of Clinical Immunology, 2022
Stelios Vlachiotis, Hassan Abolhassani
Germinal centers are the microanatomical structures that regulate B cell functions and provide the essential cues to promote B cell survival, proliferation, differentiation, and Ig production [3,15]. Physiologically, a complex network of extracellular stimuli is physically restricted inside the GC to induce a plethora of signaling pathways and promote essential (biological) processes, including TF-mediated induction of CSR. The four main driving forces for the CSR during GC B cells differentiation are as follows: external signals of B cell receptors (BCR, by antigen engagement), T cell co-stimulators (mainly tumor necrosis factor [TNF] superfamily receptors CD40L/CD40 and ICOS/ICOSL), T cell cytokine/interleukin receptors (mainly IL-21R and IL-4R), and pattern recognition receptors (mainly Toll-like receptors, TLRs) [9,15–17]. Other B cell cross-activation via survival signals (e.g. B-cell activating factor [BAFF] and A proliferation-inducing ligand [APRIL] stimulating TNF receptors superfamily 13B/C) and Ig receptors (e.g. fragment constant region [Fc] receptors) seems to be dispensable for the CSR process [18].