Adaptive immune response: Antigens, lymphocytes, and accessory cells
Gabriel Virella in Medical Immunology, 2019
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.
Mucosal B cells and their function
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
When B-cell activation occurs in a primary follicle where there is no existing germinal center, the proliferation of B cells activated with cognate T-cell help generates a cluster of large cells, precursors of a mature germinal center. The cluster of dividing cells nudges the naive B-cell component of a primary follicle aside to form the mantle component of a secondary follicle. This effect has been demonstrated to occur within the first few days of life in human Peyer's patches, which invariably contain germinal centers throughout life. This scenario may differ with colonic isolated lymphoid follicles, which frequently lack germinal centers.
Positive Selection of B-Cell Repertoire, Idiotype Networks and Immunological Memory
Maurizio Zanetti, J. Donald Capra in The Antibodies, 2002
The concepts of idiotype networks have been removed from recent texbooks. So it was a pleasant surprise to read the following in a recent paper of C.A. Janeway [6]: "Jerne's idiotypic network actually can act on the naive B-cell repertoire to positively select certain heavy/light chain pairs over others." This is exactly what was proposed by A. Coutinho and ourselves, among others, many years ago [7-9]. Will idiotypic networks enjoy a vivid revival like suppressor T-cells?
Targeting the N332-supersite of the HIV-1 envelope for vaccine design
Published in Expert Opinion on Therapeutic Targets, 2020
Thandeka Moyo, Dale Kitchin, Penny L. Moore
Lastly, Steichen et al. (2019) developed a priming immunogen engineered to bind to BG18-like antibodies. Using directed evolution, the researchers created modified trimer priming immunogens which were bound with high affinity by a variety of antibodies with BG18-like CDRH3 features, using different VH and VL genes, identified from repertoires of diverse HIV-1-uninfected donors [80]. This approach aimed to mitigate the dependence of N332 germline-targeting on the presence of precursors with specific CDRH3 sequences, to increase the chances of relevant B cells being activated upon vaccination, and has potential applications for other pathogens where bNAbs depend on CDRH3 interactions. The modified priming immunogens were shown to bind to potential BG18-like human naive B cells ex vivo, with an N332-specific naive B cell isolation frequency of approximately 0.001% [80]. This is a comparable frequency to that of precursors engaged by the CD4bs directed immunogen eOD-GT8 [93]. In the context of a human B cell repertoire estimated to be between 1012–1018 this may be biologically plausible for vaccine design [98]. This study further suggests that eliciting N332-supersite-specific responses upon vaccination may be an achievable goal in a prime-boost scenario.
Effect of high mobility group box 1 on Toll-like receptor 9 in B cells in myeloperoxidase-ANCA-associated vasculitis
Published in Autoimmunity, 2020
Chen Wang, Hui Deng, Yan Gong, Ran You, Min Chen, Ming-Hui Zhao
Masum et al. assumed that overexpression of TLR9 correlates with podocyte injury and development of autoimmune membranoproliferative glomerulonephritis [23]. Papadimitraki et al. found that TLR9 expression in B cells increased significantly in patients with active systemic lupus erythematosus compared with those in remission [24]. In AAV, the association between TLR9 expression and disease activity of AAV was first confirmed in the current study, which extended the role of TLR9 in the pathogenesis of AAV. On the one hand, it is conceivable that functions of B cells could be mediated by multiple activation pathways through BCR, CD40, or TLRs [25]. However, evidence suggested that human naive B cell could be activated by TLR9 stimulation [26]. In a recent study, Gestermann et al. suggested that mammal DNA from human neutrophil extracellular traps could bind to TLR9 and induce B cell activation and proliferation [27]. On the other hand, it was reported that TLR9 stimulation with CpG-ODN, the ligand for TLR9, plus BCR activation could increase autoantibody production [14–16] and upregulate TLR9 expression in B cells [28], which might result in a positive feedback effect on the function of B cell. These were in line with the findings of Suzuki et al., who demonstrated that the transcription level of TLR9 was elevated depending on the severity of IgA nephropathy and correlated with the degree of urinary albuminuria and serum IgA level in severe cases [29].
Comparison of the deep immune profiling of B cell subsets between healthy adults and Sjögren’s syndrome
Published in Annals of Medicine, 2022
Ruiling Feng, Jing Zhao, Feng Sun, Miao Miao, Xiaolin Sun, Jing He, Zhanguo Li
To analyse the changes of B cell subpopulations related to ages, peripheral blood samples were drawn from healthy adults of various age groups performed by flow cytometry. Data showed that there was no significant difference among those five groups of total B cells (proportion: r = 0.130, p=.170; counts: r = 0.095, p=.314; Figure 2(A), Figure S1A). The age-related changes were expressed that the proportions and absolute counts of naive B cell were considered to go up with increasing age (proportion: r = 0.295, p=.001; counts: r = 0.187, p=.046; Figure 2(B), Figure S1B). In contrast, our analysis demonstrated that the proportions of unswitched memory B cells reduced strikingly, especially in individuals ≥40 years old and DN B cells had a tendency to decline with age although both did not reach significance (unswitched memory B cells: r=–0.147, p=.118; DN B cells: r=–0.141, p=.136; Figure 2(C,I)). Besides, the percentage of switched memory B cells and B10 cells experienced a striking decrease with age (switched memory B cells: r=–0.210, p=.025; B10 cells: r=–0.292, p=.002; Figure 2(D,H)). These differences throughout life highlights the importance of creating age specific reference patterns. Furthermore, we also observed that the percentage of CD19 + CD20+ B cells together with CD19 + CD20– B cells, plasma cells, exhibited a decrease but not significant effect by age among the groups (CD19 + CD20+ B cells: r=–0.050; CD19 + CD20– B cells: r=–0.030; plasma cells: r=–0.088; p>.05; Figure 2(E,F,G)).