PI3K- and PTEN-Governed PIP2 and PIP3 Equilibrium Regulates the Activation and Function of B Cells Through Dock2 Controlled Growth of Antigen Receptor Microclusters

2018 ◽  
Author(s):  
Jing Wang ◽  
Liling Xu ◽  
Samina Shaheen ◽  
Sichen Liu ◽  
Wanli Liu
Keyword(s):  
B Cells ◽  
Antigen Receptor ◽  
Controlled Growth ◽  
And Function

scholarly journals The Development and Function of Regulatory B Cells Expressing IL-10 (B10 Cells) Requires Antigen Receptor Diversity and TLR Signals

2009 ◽  
Vol 182 (12) ◽  
pp. 7459-7472 ◽  
Author(s):  
Koichi Yanaba ◽  
Jean-David Bouaziz ◽  
Takashi Matsushita ◽  
Takeshi Tsubata ◽  
Thomas F. Tedder
Keyword(s):  
B Cells ◽  
Antigen Receptor ◽  
Regulatory B Cells ◽  
And Function ◽  
B10 Cells

scholarly journals Hide and seek: interplay between influenza viruses and B cells

2020 ◽  
Vol 32 (9) ◽  
pp. 605-611 ◽  
Author(s):  
Masayuki Kuraoka ◽  
Yu Adachi ◽  
Yoshimasa Takahashi
Keyword(s):  
B Cells ◽  
B Cell ◽  
Surface Protein ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Native Structure ◽  
Humoral Immune ◽  
Protective Antibodies ◽  
Major Surface ◽  
And Function

Abstract Influenza virus constantly acquires genetic mutations/reassortment in the major surface protein, hemagglutinin (HA), resulting in the generation of strains with antigenic variations. There are, however, HA epitopes that are conserved across influenza viruses and are targeted by broadly protective antibodies. A goal for the next-generation influenza vaccines is to stimulate B-cell responses against such conserved epitopes in order to provide broad protection against divergent influenza viruses. Broadly protective B cells, however, are not easily activated by HA antigens with native structure, because the virus has multiple strategies to escape from the humoral immune responses directed to the conserved epitopes. One such strategy is to hide the conserved epitopes from the B-cell surveillance by steric hindrance. Technical advancement in the analysis of the human B-cell antigen receptor (BCR) repertoire has dissected the BCRs to HA epitopes that are hidden in the native structure but are targeted by broadly protective antibodies. We describe here the characterization and function of broadly protective antibodies and strategies that enable B cells to seek these hidden epitopes, with potential implications for the development of universal influenza vaccines.

scholarly journals B Cells in T Follicular Helper Cell Development and Function: Separable Roles in Delivery of ICOS Ligand and Antigen

2014 ◽  
Vol 192 (7) ◽  
pp. 3166-3179 ◽  
Author(s):  
Jason S. Weinstein ◽  
Sarah A. Bertino ◽  
Sairy G. Hernandez ◽  
Amanda C. Poholek ◽  
Taylor B. Teplitzky ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Development ◽  
Helper Cell ◽  
Follicular Helper ◽  
T Follicular Helper Cell ◽  
And Function

scholarly journals WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4139-4147 ◽  
Author(s):  
Lisa S. Westerberg ◽  
Miguel A. de la Fuente ◽  
Fredrik Wermeling ◽  
Hans D. Ochs ◽  
Mikael C. I. Karlsson ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Marginal Zone ◽  
Hematopoietic Cells ◽  
Selective Advantage ◽  
Relative Contribution ◽  
B Cell Homeostasis ◽  
And Function

Abstract Development of hematopoietic cells depends on a dynamic actin cytoskeleton. Here we demonstrate that expression of the cytoskeletal regulator WASP, mutated in the Wiskott-Aldrich syndrome, provides selective advantage for the development of naturally occurring regulatory T cells, natural killer T cells, CD4+ and CD8+ T lymphocytes, marginal zone (MZ) B cells, MZ macrophages, and platelets. To define the relative contribution of MZ B cells and MZ macrophages for MZ development, we generated wild-type and WASP-deficient bone marrow chimeric mice, with full restoration of the MZ. However, even in the presence of MZ macrophages, only 10% of MZ B cells were of WASP-deficient origin. We show that WASP-deficient MZ B cells hyperproliferate in vivo and fail to respond to sphingosine-1-phosphate, a crucial chemoattractant for MZ B-cell positioning. Abnormalities of the MZ compartment in WASP−/− mice lead to aberrant uptake of Staphylococcus aureus and to a reduced immune response to TNP-Ficoll. Moreover, WASP-deficient mice have increased levels of “natural” IgM antibodies. Our findings reveal that WASP regulates both development and function of hematopoietic cells. We demonstrate that WASP deficiency leads to an aberrant MZ that may affect responses to blood-borne pathogens and peripheral B-cell tolerance.

Loss of IP3 Receptor–Mediated Ca2+ Release in Mouse B Cells Results in Abnormal B Cell Development and Function

2017 ◽  
Vol 199 (2) ◽  
pp. 570-580 ◽  
Author(s):  
Huayuan Tang ◽  
Hong Wang ◽  
Qingsong Lin ◽  
Feifei Fan ◽  
Fei Zhang ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Development ◽  
B Cell Development ◽  
Ip3 Receptor ◽  
And Function

scholarly journals The B-cell tumor–associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor

Blood ◽  
2010 ◽  
Vol 116 (22) ◽  
pp. 4532-4541 ◽  
Author(s):  
Michael Hudecek ◽  
Thomas M. Schmitt ◽  
Sivasubramanian Baskar ◽  
Maria Teresa Lupo-Stanghellini ◽  
Tetsuya Nishida ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Chimeric Antigen Receptor ◽  
Cell Lymphoma ◽  
Embryonic Stem ◽  
Antigen Receptor ◽  
Orphan Receptor ◽  
Mantle Cell

Monoclonal antibodies and T cells modified to express chimeric antigen receptors specific for B-cell lineage surface molecules such as CD20 exert antitumor activity in B-cell malignancies, but deplete normal B cells. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) was identified as a highly expressed gene in B-cell chronic lymphocytic leukemia (B-CLL), but not normal B cells, suggesting it may serve as a tumor-specific target for therapy. We analyzed ROR1-expression in normal nonhematopoietic and hematopoietic cells including B-cell precursors, and in hematopoietic malignancies. ROR1 has characteristics of an oncofetal gene and is expressed in undifferentiated embryonic stem cells, B-CLL and mantle cell lymphoma, but not in major adult tissues apart from low levels in adipose tissue and at an early stage of B-cell development. We constructed a ROR1-specific chimeric antigen receptor that when expressed in T cells from healthy donors or CLL patients conferred specific recognition of primary B-CLL and mantle cell lymphoma, including rare drug effluxing chemotherapy resistant tumor cells that have been implicated in maintaining the malignancy, but not mature normal B cells. T-cell therapies targeting ROR1 may be effective in B-CLL and other ROR1-positive tumors. However, the expression of ROR1 on some normal tissues suggests the potential for toxi-city to subsets of normal cells.

scholarly journals Ligand-independent Signaling Functions for the B Lymphocyte Antigen Receptor and Their Role in Positive Selection during B Lymphopoiesis

2001 ◽  
Vol 194 (11) ◽  
pp. 1583-1596 ◽  
Author(s):  
Gregory Bannish ◽  
Ezequiel M. Fuentes-Pananá ◽  
John C. Cambier ◽  
Warren S. Pear ◽  
John G. Monroe
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Antigen Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
B Lymphopoiesis ◽  
Biologically Relevant ◽  
Developmental Progression

Signal transduction through the B cell antigen receptor (BCR) is determined by a balance of positive and negative regulators. This balance is shifted by aggregation that results from binding to extracellular ligand. Aggregation of the BCR is necessary for eliciting negative selection or activation by BCR-expressing B cells. However, ligand-independent signaling through intermediate and mature forms of the BCR has been postulated to regulate B cell development and peripheral homeostasis. To address the importance of ligand-independent BCR signaling functions and their regulation during B cell development, we have designed a model that allows us to isolate the basal signaling functions of immunoglobulin (Ig)α/Igβ-containing BCR complexes from those that are dependent upon ligand-mediated aggregation. In vivo, we find that basal signaling is sufficient to facilitate pro-B → pre-B cell transition and to generate immature/mature peripheral B cells. The ability to generate basal signals and to drive developmental progression were both dependent on plasma membrane association of Igα/Igβ complexes and intact immunoregulatory tyrosine activation motifs (ITAM), thereby establishing a correlation between these processes. We believe that these studies are the first to directly demonstrate biologically relevant basal signaling through the BCR where the ability to interact with both conventional as well as nonconventional extracellular ligands is eliminated.

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