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New Insight into B Cell Biology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 8672

Special Issue Editor


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Guest Editor
Department of Immunology, Eötvös Loránd University, 1117 Budapest, Hungary
Interests: regulation of the immune response; B cells; signaling; receptor cross-talk; regulatory cells; autoimmunity; rheumatoid arthritis
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Special Issue Information

Dear Colleagues,

B cells play a critical role in the development of an immune response. After encountering antigens, B cells differentiate into plasma cells, secreting high-affinity antibodies or memory B cells, providing long-lasting memory. B cells also present antigens to T cells, initiating the T cell response to cognate antigens, produce cytokines, and regulate the immune responses. During their development, B cells are educated to differentiate self from non-self, and thus, they go through several checkpoints controlled by B cell receptors and influenced by innate immune sensors such as toll-like receptors. These processes lead to efficient immune response and protection against invading pathogens while maintaining tolerance against self. In the last decade, deep immune phenotyping of developing B cells has led to the discovery of novel B cell subsets, some of them having a role in B cell pathologies, such as autoimmune and infectious diseases or cancer. Targeting these B cells might be a challenge for developing novel therapies.

B cell development is under the control of different metabolic programs, from the precursor states in the bone marrow to the terminal plasma cell and memory cell differentiation. Revealing metabolic programs of B cells may lead to a better understanding of B cell development and the diverse functions of various subsets, as well as B cell disfunctions causing malignancies and autoimmune diseases.

Regulatory B cells suppress inappropriate immune responses and support immune tolerance through direct cell-to-cell contact and/or through the production of cytokines such as IL-10, TGFβ or IL-35. Dysfunction of Bregs might contribute to the development of autoimmune diseases, uncontrolled inflammation, or tumors. However, little is known about the intracellular pathways, leading to their differentiation and the incidence of metabolic programs. Recent observations highlight the glucose metabolism as an essential factor for the expansion of Breg cells.

Accumulating evidence has revealed that B cells play a dual role in tumor immunity; however, detailed characterization of the relationship between B cells and tumors is urgently needed, as a prerequisite for the development of B-cell-based immunotherapies.

The goal of this Special Issue is to highlight the latest progress achieved in these exciting areas of B cell research in health and disease. Up-to-date review articles and experimental papers are welcome.

Prof. Dr. Gabriella Sármay
Guest Editor

Manuscript Submission Information

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Keywords

  • B cells
  • B cell targeting
  • novel subsets
  • metabolism
  • immune regulation
  • tumour immunity

Published Papers (4 papers)

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Research

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14 pages, 2479 KiB  
Article
B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection
by Gina Marie Uehre, Svetlana Tchaikovski, Atanas Ignatov, Ana Claudia Zenclussen and Mandy Busse
Int. J. Mol. Sci. 2023, 24(22), 16091; https://doi.org/10.3390/ijms242216091 - 8 Nov 2023
Cited by 2 | Viewed by 1070
Abstract
The maternal balance between B regulatory (Breg) cells and inflammatory B cells is of central importance for protection against preterm birth (PTB). However, the impact of B cell signaling in early maternal and fetal immune responses on inflammatory insults remains underinvestigated. To understand [...] Read more.
The maternal balance between B regulatory (Breg) cells and inflammatory B cells is of central importance for protection against preterm birth (PTB). However, the impact of B cell signaling in early maternal and fetal immune responses on inflammatory insults remains underinvestigated. To understand which role B cells and B-cell-specific signaling play in the pathogenesis of PTB, the later was induced by an injection of LPS in B cell-sufficient WT mice, CD19−/−, BMyD88−/− and µMT murine dams at gestational day 16 (gd 16). WT dams developed a strong inflammatory response in their peritoneal cavity (PC), with an increased infiltration of granulocytes and enhanced IL-6, TNF-α, IL-17 and MCP-1 levels. However, they demonstrated a reduced NOS2 expression of PC macrophages 4 h after the LPS injection. Simultaneously, LPS-challenged WT dams upregulated pregnancy-protective factors like IL-10 and TARC. The concentrations of inflammatory mediators in the placental supernatants, amniotic fluids, fetal serums and gestational tissues were lower in LPS-challenged WT dams compared to CD19−/−, BMyD88−/− and µMT dams, thereby protecting WT fetuses from being born preterm. B cell deficiency, or the loss of B-cell-specific CD19 or MyD88 expression, resulted in an early shift from immune regulation towards inflammation at the fetomaternal interface and fetuses, resulting in PTB. Full article
(This article belongs to the Special Issue New Insight into B Cell Biology)
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21 pages, 6194 KiB  
Article
An Optimized Flow Cytometric Method to Demonstrate the Differentiation Stage-Dependent Ca2+ Flux Responses of Peripheral Human B Cells
by Anna Bajnok, Timea Serény-Litvai, Viktória Temesfői, Jasper Nörenberg, Róbert Herczeg, Ambrus Kaposi, Timea Berki and Emese Mezosi
Int. J. Mol. Sci. 2023, 24(10), 9107; https://doi.org/10.3390/ijms24109107 - 22 May 2023
Cited by 2 | Viewed by 2969
Abstract
Calcium (Ca2+) flux acts as a central signaling pathway in B cells, and its alterations are associated with autoimmune dysregulation and B-cell malignancies. We standardized a flow-cytometry-based method using various stimuli to investigate the Ca2+ flux characteristics of circulating human [...] Read more.
Calcium (Ca2+) flux acts as a central signaling pathway in B cells, and its alterations are associated with autoimmune dysregulation and B-cell malignancies. We standardized a flow-cytometry-based method using various stimuli to investigate the Ca2+ flux characteristics of circulating human B lymphocytes from healthy individuals. We found that different activating agents trigger distinct Ca2+ flux responses and that B-cell subsets show specific developmental-stage dependent Ca2+ flux response patterns. Naive B cells responded with a more substantial Ca2+ flux to B cell receptor (BCR) stimulation than memory B cells. Non-switched memory cells responded to anti-IgD stimulation with a naive-like Ca2+ flux pattern, whereas their anti-IgM response was memory-like. Peripheral antibody-secreting cells retained their IgG responsivity but showed reduced Ca2+ responses upon activation, indicating their loss of dependence on Ca2+ signaling. Ca2+ flux is a relevant functional test for B cells, and its alterations could provide insight into pathological B-cell activation development. Full article
(This article belongs to the Special Issue New Insight into B Cell Biology)
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24 pages, 5401 KiB  
Article
ArtinM Cytotoxicity in B Cells Derived from Non-Hodgkin’s Lymphoma Depends on Syk and Src Family Kinases
by Bruno Rafael Barboza, Sandra Maria de Oliveira Thomaz, Airton de Carvalho Junior, Enilza Maria Espreafico, Jackson Gabriel Miyamoto, Alexandre Keiji Tashima, Maurício Frota Camacho, André Zelanis, Maria Cristina Roque-Barreira and Thiago Aparecido da Silva
Int. J. Mol. Sci. 2023, 24(2), 1075; https://doi.org/10.3390/ijms24021075 - 5 Jan 2023
Cited by 1 | Viewed by 2268
Abstract
Receptors on the immune cell surface have a variety of glycans that may account for the immunomodulation induced by lectins, which have a carbohydrate recognition domain (CRD) that binds to monosaccharides or oligosaccharides in a specific manner. ArtinM, a D-mannose-binding lectin obtained from [...] Read more.
Receptors on the immune cell surface have a variety of glycans that may account for the immunomodulation induced by lectins, which have a carbohydrate recognition domain (CRD) that binds to monosaccharides or oligosaccharides in a specific manner. ArtinM, a D-mannose-binding lectin obtained from Artocarpus heterophyllus, has affinity for the N-glycans core. Immunomodulation by ArtinM toward the Th1 phenotype occurs via its interaction with TLR2/CD14 N-glycans on antigen-presenting cells, as well as recognition of CD3γ N-glycans on murine CD4+ and CD8+ T cells. ArtinM exerts a cytotoxic effect on Jurkat human leukemic T-cell line and human myeloid leukemia cell line (NB4). The current study evaluated the effects of ArtinM on murine and human B cells derived from non-Hodgkin’s lymphoma. We found that murine B cells are recognized by ArtinM via the CRD, and the ArtinM stimulus did not augment the proliferation rate or production of IL-2. However, murine B cell incubation with ArtinM augmented the rate of apoptosis, and this cytotoxic effect of ArtinM was also seen in human B cell-lines sourced from non-Hodgkin’s lymphoma Raji cell line. This cytotoxic effect was inhibited by the phosphatase activity of CD45 on Lck, and the protein kinases of the Src family contribute to cell death triggered by ArtinM. Full article
(This article belongs to the Special Issue New Insight into B Cell Biology)
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Review

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15 pages, 1552 KiB  
Review
Breg-Mediated Immunoregulation in the Skin
by Elina A. Zheremyan, Alina S. Ustiugova, Nina M. Karamushka, Aksinya N. Uvarova, Ekaterina M. Stasevich, Apollinariya V. Bogolyubova, Dmitry V. Kuprash and Kirill V. Korneev
Int. J. Mol. Sci. 2024, 25(1), 583; https://doi.org/10.3390/ijms25010583 - 2 Jan 2024
Cited by 1 | Viewed by 1584
Abstract
Wound healing is a complex process involving a coordinated series of events aimed at restoring tissue integrity and function. Regulatory B cells (Bregs) are a subset of B lymphocytes that play an essential role in fine-tuning immune responses and maintaining immune homeostasis. Recent [...] Read more.
Wound healing is a complex process involving a coordinated series of events aimed at restoring tissue integrity and function. Regulatory B cells (Bregs) are a subset of B lymphocytes that play an essential role in fine-tuning immune responses and maintaining immune homeostasis. Recent studies have suggested that Bregs are important players in cutaneous immunity. This review summarizes the current understanding of the role of Bregs in skin immunity in health and pathology, such as diabetes, psoriasis, systemic sclerosis, cutaneous lupus erythematosus, cutaneous hypersensitivity, pemphigus, and dermatomyositis. We discuss the mechanisms by which Bregs maintain tissue homeostasis in the wound microenvironment through the promotion of angiogenesis, suppression of effector cells, and induction of regulatory immune cells. We also mention the potential clinical applications of Bregs in promoting wound healing, such as the use of adoptive Breg transfer. Full article
(This article belongs to the Special Issue New Insight into B Cell Biology)
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