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Adaptive immune response: Antigens, lymphocytes, and accessory cells
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, John W. Sleasman
In the case of the stimulation of a B-cell response with a T-dependent antigen, the additional signals are delivered by helper T cells in the form of cytokines and interactions with costimulatory molecules expressed by T cells. A naive B cell is initially stimulated by recognition of an epitope of the immunogen through the BCR. Two other sets of membrane molecules are involved in this initial activation, the main one being the CD19/CD21/CD81/Leu-13 B-cell coreceptor complex. The activation of CD19 enhances the activating effect of the occupancy of the BCR. CD21, activated by C3 fragments, is the basis for enhanced B-cell activation resulting from complement activation.
Pathogenesis
Published in Aparna Palit, Arun C. Inamadar, Systemic Sclerosis, 2019
The polymorphisms involving CD19 and CD22 have been reported to increase the susceptibility to SSc. CD19, a strong positive regulator of B cells, is over-expressed in SSc.18 In animal experiments, it has been demonstrated that the CD19 overexpression results in spontaneous antibody production.19 It causes a breakdown of peripheral tolerance of B cells leading to autoimmunity. In the peripheral blood of patients with SSc, naïve B cells are greater in number and there is a depletion of memory B cells/early plasma cells due to apoptosis. However, overexpression of CD19 on memory B cells enhances their ability to produce immunoglobulin. Chronic activation of remaining memory B cells by CD19 leads to production of autoantibodies.18 The autoantibodies in SSc are involved in fibrosis through activation of fibroblasts or inhibition of matrix metalloproteinases (MMP). These also target PDGF-receptor, fibrillin, MMP-1, MMP-6, endothelin Type A receptor, and angiotensin receptor. The latter two act as agonists causing vasoconstriction and fibroblast activation.19
Potential of Antibody Therapy for Respiratory Virus Infections
Published in Sunit K. Singh, Human Respiratory Viral Infections, 2014
Tze-Minn Mak, Ruisi Hazel Lin, Yee-Joo Tan
As an alternative to B cell immortalization, specific mAbs may be obtained by screening from recombinant antibody libraries that constitute the genetic diversity of the human antibody repertoire. In the human immune system, diversity in antibody binding is achieved by the combinatorial assembly of germline segments (V(D)J recombination). This produces a naïve B cell repertoire, each expressing a unique antibody-binding site on their surface. Exposure to antigen selects from this repertoire and affinity for the particular antigen is achieved by somatic hypermutations (SHM) in the CDR regions of the variable antibody chains (a process also known as affinity maturation). Additional mechanisms such as (i) nonstandard recombinations, (ii) SHM-associated genetic insertions and deletions, and (iii) affinity maturation and direct antigen contact by non-CDR antibody regions also contribute to the diversity within the antibody repertoire [50].
Advances in biological and targeted therapies for systemic sclerosis
Published in Expert Opinion on Biological Therapy, 2023
Erica Mulcaire-Jones, Andrea Hsiu Ling Low, Robyn Domsic, Michael L Whitfield, Dinesh Khanna
B cells, in addition to autoantibody production, mediate antigen presentation, cytokine production, T cell differentiation, and dendritic cell function via cytokine production and activation of T cells [13]. Several lines of evidence point toward B-cell abnormalities in the immune dysregulation of SSc; (i) SSc-specific autoantibodies strongly associate with distinct disease phenotypes; (ii) B cell infiltrates are observed in SSc skin lesions and SSc-ILD; (iii) gene expression of SSc skin lesions revealed upregulation of B cell-related genes; (iv) circulating naïve B cells were found to be increased, while memory B cells, though reduced in numbers, were shown to be hyperactive leading to increased antibody formation; (v) serum BAFF was found to be elevated in SSc patients versus healthy controls and correlated with severity of skin fibrosis; and (vi) BAFF mRNA expression was upregulated in lesional skin of patients with early versus late dcSSc [14,83–86].
Mechanisms of cellular and humoral immunity through the lens of VLP-based vaccines
Published in Expert Review of Vaccines, 2022
Hunter McFall-Boegeman, Xuefei Huang
Naïve B cells reside mainly in the spleen and lymph nodes. In order to activate them, vaccines must be targeted to the lymphatic tissue. As discussed earlier, the sizes of VLPs are well situated to track to lymph nodes (Figure 1b). VLP<apos;>s fate can be further controlled by the method of administration. Cubas et al. utilized SHIV VLPs (SIV Gag + HIV SF162 Env) to test the immune responses following injections at various common injection sites[99]. VLPs were labeled with an IR dye and lymph nodes were harvested 24 hr post injection. Intraperitoneal injection showed no VLPs in the lymph nodes and the amount of VLP in the lymph nodes increased going from subcutaneous to intramuscular and finally intradermal injection. The intradermal injection had detectable VLP levels in all four lymph nodes harvested. VLP levels in the lymph node correlated positively with the IgG titers and CTL efficacy. Therefore, caution should be taken when comparing immune responses across various studies. A relatively weak immune response could be due to the choice of the injection method and the resulting fate of VLPs tracking to lymph nodes. Additionally, the injection method can skew the class of Ig elicited. Intranasal immunization using a Qß-based vaccine against influenza was the only immunization method that elicited strong local IgA titers in the lung[138].
Cholangiocarcinoma: what are the most valuable therapeutic targets – cancer-associated fibroblasts, immune cells, or beyond T cells?
Published in Expert Opinion on Therapeutic Targets, 2021
Juan Wang, Emilien Loeuillard, Gregory J. Gores, Sumera I. Ilyas
In contrast to T lymphocytes, the role of B lymphocytes in CCA development and progression is far less clear. B cells have an integral role in humoral immunity via the production of immunoglobulins. Upon antigen recognition, naïve B cells become activated B cells and subsequently differentiate into plasma cells, which are capable of antibody production [86]. There are several subsets of B lymphocytes, including pro-tumor or regulatory B cells that can dampen the antitumor immune response and promote tumorigenesis. In pancreatic ductal adenocarcinoma, IL-35 producing B cells stimulated tumor cell proliferation [87]. This B cell subset was recruited to the tumor by the chemoattractant CXCL-13, and CXCL13 blockade resulted in a decline in this population with reduction of tumor growth [87]. Although these findings imply that B cell–based immunotherapeutic approaches may hold promise, the role of B lymphocytes in CCA has yet to be elucidated.