scholarly journals B cell activation. III. B cell plasma membrane depolarization and hyper-Ia antigen expression induced by receptor immunoglobulin cross-linking are coupled.

1983 ◽  
Vol 158 (5) ◽  
pp. 1589-1599 ◽  
Author(s):  
J G Monroe ◽  
J C Cambier
Keyword(s):  
Plasma Membrane ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Antigen Expression ◽  
Membrane Depolarization ◽  
Cell Surface Expression ◽  
Cross Linking ◽  
Cell Plasma Membrane ◽  
Cell Plasma

We report investigation of the relationship between ligand-induced B cell plasma membrane depolarization and increased expression of membrane-associated, I-A subregion encoded (mI-A) antigens. Results demonstrate that equal frequencies of B cells are stimulated to undergo membrane depolarization and to increase mI-A expression in response to mitogen, anti-Ig, and thymus-independent (TI) or thymus-dependent (TD) antigens. Further, a cause-and-effect relationship between these two events is suggested by results that demonstrate that inhibition of anti-Fab--induced depolarization by valinomycin also inhibits the subsequent increase in mI-A antigen expression and "passive" (non-ligand-mediated) depolarization of murine B cells by K+ results in hyper-mI-A antigen expression. Based upon these results we hypothesize that antigen-mediated receptor cross-linking results in signal transduction via membrane depolarization, which is resultant in increased mI-A antigen synthesis and cell surface expression. This increase in mI-A antigen density may render the B cell more receptive to subsequent interaction with I-region-restricted helper T cells.

scholarly journals B cell activation. I. Anti-immunoglobulin-induced receptor cross-linking results in a decrease in the plasma membrane potential of murine B lymphocytes.

1983 ◽  
Vol 157 (6) ◽  
pp. 2073-2086 ◽  
Author(s):  
J G Monroe ◽  
J C Cambier
Keyword(s):  
Cell Cycle ◽  
Plasma Membrane ◽  
Membrane Potential ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Membrane Depolarization ◽  
Cross Linking ◽  
Thymidine Uptake ◽  
Plasma Membrane Potential

We report analyses of the effect of anti-Fab antibodies on plasma membrane potential of mouse B lymphocytes. Results indicate that divalent fragments of anti-Fab antibodies mitogenic for B cells stimulate membrane depolarization detectable by cytofluorometric analysis of 3,3'-dipentyloxacarbocyanine iodide-stained cells. Depolarization is detectable within 5 min of exposure to ligand and maximal within 1 h of exposure when greater than or equal to 80% of splenic B cells exhibit decreased membrane potential. The ineffectiveness of monovalent Fab antibody fragments in inducing this event suggests that receptor immunoglobulin cross-linking is essential. Frequencies of cells induced to enter cell cycle, as assessed by acridine orange cell cycle analysis, are equal to those induced to depolarize by lipopolysaccharide plus dextran sulfate or anti-Fab, which suggests a relationship between these events. However, membrane depolarization is itself an insufficient signal to promote subsequent thymidine uptake, as evidenced by the fact that doses of anti-Fab that are suboptimal for thymidine uptake induce maximal depolarization. These results suggest that cross-linking of surface immunoglobulin on B cells may provide an initial signal for activation but is itself insufficient to drive B cell proliferation.

scholarly journals AB0024 IN VITRO CHARACTERIZATION OF CENERIMOD, A POTENT AND SELECTIVE SPHINGOSINE 1-PHOSPHATE RECEPTOR 1 (S1P1) MODULATOR IN PREVENTING MIGRATION OF NON-ACTIVATED AND ACTIVATED PRIMARY HUMAN B CELLS IN THE PRESENCE OR ABSENCE OF GLUCOCORTICOIDS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1046.1-1046
Author(s):  
L. Schlicher ◽  
P. Kulig ◽  
M. Murphy ◽  
M. Keller
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
B Cell Activation ◽  
Human B Cells ◽  
Circulating Lymphocytes

Background:Cenerimod is a potent, selective, and orally active sphingosine 1-phosphate receptor 1 (S1P1) modulator that is currently being evaluated in a Phase 2b study in patients with systemic lupus erythematosus (SLE) (NCT03742037). S1P1 receptor modulators sequester circulating lymphocytes within lymph nodes, thereby reducing pathogenic autoimmune cells (including B lymphocytes) in the blood stream and in inflamed tissues. Extensive clinical experience has become available for the nonselective S1P receptor modulator fingolimod in relapsing forms of multiple sclerosis, supporting this therapeutic concept for the treatment of autoimmune disorders.Objectives:Although the effect of S1P-receptor modulators in reducing peripheral B cells is well documented1,2, the role of the S1P1 receptor on this cell type is only incompletely understood. In this study, the mode of action of cenerimod on primary human B cells was investigated in a series of in vitro experiments, including S1P1 receptor cell surface expression and chemotaxis towards S1P. Moreover, S1P1 expression following B cell activation in vitro was studied. As glucocorticoids (GC) are frequently used in the treatment of patients with autoimmune disorders including SLE, the potential influence of GC on the mode of action of cenerimod was evaluated.Methods:Primary human B lymphocytes from healthy donors were isolated from whole blood. In one set of experiments, cells were treated with different concentrations of cenerimod to measure S1P1 receptor internalization by flow cytometry. In a second set of experiments, isolated B cells were activated using different stimuli or left untreated. Cells were then analysed for S1P1 and CD69 cell surface expression and tested in a novel real-time S1P-mediated migration assay. In addition, the effect of physiological concentrations of GCs (prednisolone and prednisone) on cenerimod activity in preventing S1P mediated migration was tested.Results:In vitro, cenerimod led to a dose-dependent internalization of the S1P1 receptor on primary human B lymphocytes. Cenerimod also blocked migration of nonactivated and activated B lymphocytes towards S1P in a concentration-dependent manner, which is in line with the retention of lymphocytes in the lymph node and the reduction of circulating lymphocytes observed in the clinical setting. Upon B cell activation, which was monitored by CD69 upregulation, a simultaneous downregulation of S1P1 expression was detected, leading to less efficient S1P-directed cell migration. Importantly, physiological concentrations of GC did not affect the inhibitory activity of cenerimod on B cell migration.Conclusion:These results show that cenerimod, by modulating S1P1, blocks B lymphocyte migration towards its natural chemoattractant S1P and demonstrate compatibility of cenerimod with GC. These results are consistent with results of comparable experiments done previously using primary human T lymphocytes.References:[1]Nakamura M et al., Mult Scler. 2014 Sep; 20(10):1371-80.[2]Strasser DS et al., RMD Open 2020;6:e001261.Disclosure of Interests:None declared

scholarly journals Carbohydrate-dependent B cell activation by fucose-binding bacterial lectins

2019 ◽  
Vol 12 (571) ◽  
pp. eaao7194 ◽  
Author(s):  
Isabel Wilhelm ◽  
Ella Levit-Zerdoun ◽  
Johanna Jakob ◽  
Sarah Villringer ◽  
Marco Frensch ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Activation ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
B Cell Activation ◽  
Intracellular Ca ◽  
Bacterial Lectins

Bacterial lectins are typically multivalent and bind noncovalently to specific carbohydrates on host tissues to facilitate bacterial adhesion. Here, we analyzed the effects of two fucose-binding lectins, BambL fromBurkholderia ambifariaand LecB fromPseudomonas aeruginosa, on specific signaling pathways in B cells. We found that these bacterial lectins induced B cell activation, which, in vitro, was dependent on the cell surface expression of the B cell antigen receptor (BCR) and its co-receptor CD19, as well as on spleen tyrosine kinase (Syk) activity. The resulting release of intracellular Ca2+was followed by an increase in the cell surface abundance of the activation marker CD86, augmented cytokine secretion, and subsequent cell death, replicating all of the events that are observed in vitro upon canonical and antigen-mediated B cell activation. Moreover, injection of BambL in mice resulted in a substantial, BCR-independent loss of B cells in the bone marrow with simultaneous, transient enlargement of the spleen (splenomegaly), as well as an increase in the numbers of splenic B cells and myeloid cells. Together, these data suggest that bacterial lectins can initiate polyclonal activation of B cells through their sole capacity to bind to fucose.

scholarly journals Subpopulations of B cells distinguished by cell surface expression of Ia antigens. Correlation of Ia and idiotype during activation by cloned Ia-restricted T cells.

1983 ◽  
Vol 158 (2) ◽  
pp. 265-279 ◽  
Author(s):  
K Bottomly ◽  
B Jones ◽  
J Kaye ◽  
F Jones
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Activation ◽  
Cell Surface Expression ◽  
Th Cells ◽  
Th Cell ◽  
Ia Antigens

We have investigated in vitro the induction of antibody responses to phosphorylcholine (PC) by cloned T helper (Th) cell lines. The cloned Th cells are antigen specific, in this case ovalbumin (OVA), self-Ia recognizing, and induce antibody secretion only if the hapten, PC, is physically linked to the carrier (OVA) molecule. The plaque-forming cell (PFC) response generated in the presence of cloned Th cells is idiotypically diverse with 5-40% of the secreting B cells bearing the TEPC-15 (T15) idiotype. The interaction of the cloned Th cells and unprimed B cells requires recognition of B cell surface Ia glycoproteins for all B cells activated to secrete anti-PC antibody, whether they be T15-bearing or not. More importantly, however, effective interaction between a cloned Th cell and a B cell is determined by the quantity of B cell surface Ia glycoproteins. Our results indicate that quantitative differences in B cell surface Ia antigens are directly related to B cell activation by the cloned Th cell. The high Ia density B cells are most easily activated by cloned Th cells, and these appear to be mainly non-T15-bearing. These data suggest that the failure of cloned Th cells to effectively activate T15-bearing B cells in vitro may be due to the lower relative Ia density of these B cells and therefore to their inability to interact effectively with cloned Ia-recognizing Th cells. These results imply that monoclonal T cells may distinguish between T15-bearing and non-T15-bearing B cells based on their Ia density.

Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide

Blood ◽  
2002 ◽  
Vol 99 (5) ◽  
pp. 1699-1705 ◽  
Author(s):  
Yoshinori Nagai ◽  
Rintaro Shimazu ◽  
Hirotaka Ogata ◽  
Sachiko Akashi ◽  
Katsuko Sudo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
Structural Similarity ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Cell Surface Molecule

RP105 is a B-cell surface molecule that has been recently assigned as CD180. RP105 ligation with an antibody induces B-cell activation in humans and mice, leading to proliferation and up-regulation of a costimulatory molecule, B7.2/CD86. RP105 is associated with an extracellular molecule, MD-1. RP105/MD-1 has structural similarity to Toll-like receptor 4 (TLR4)/MD-2. TLR4 signals a membrane constituent of Gram-negative bacteria, lipopolysaccharide (LPS). MD-2 is indispensable for TLR4-dependent LPS responses because cells expressing TLR4/MD-2, but not TLR4 alone, respond to LPS. RP105 also has a role in LPS responses because B cells lacking RP105 show hyporesponsiveness to LPS. Little is known, however, regarding whether MD-1 is important for RP105-dependent LPS responses, as MD-2 is for TLR4. To address the issue, we developed mice lacking MD-1 and generated monoclonal antibodies (mAbs) to the protein. MD-1–null mice showed impairment in LPS-induced B-cell proliferation, antibody production, and B7.2/CD86 up-regulation. These phenotypes are similar to those of RP105-null mice. The similarity was attributed to the absence of cell surface RP105 on MD-1–null B cells. MD-1 is indispensable for cell surface expression of RP105. A role for MD-1 in LPS responses was further studied with anti–mouse MD-1 mAbs. In contrast to highly mitogenic anti-RP105 mAbs, the mAbs to MD-1 were not mitogenic but antagonistic on LPS-induced B-cell proliferation and on B7.2 up-regulation. Collectively, MD-1 is important for RP105 with respect to B-cell surface expression and LPS recognition and signaling.

RP105 Is Associated With MD-1 and Transmits an Activation Signal in Human B Cells

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2815-2822 ◽  
Author(s):  
Yoshihiro Miura ◽  
Rintaro Shimazu ◽  
Kensuke Miyake ◽  
Sachiko Akashi ◽  
Hirotaka Ogata ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
B Cell Activation ◽  
Cell Surface Molecule ◽  
Induced Apoptosis

Abstract RP105 was originally discovered as a mouse B-cell surface molecule that transmits an activation signal. The signal leads to resistance against irradiation-induced apoptosis and massive B-cell proliferation. Recently, we found that mouse RP105 is associated with another molecule, MD-1. We have isolated here the human MD-1 cDNA. We show that human MD-1 is also associated with human RP105 and has an important role in cell surface expression of RP105. We also describe a monoclonal antibody (MoAb) that recognizes human RP105. Expression of RP105 is restricted to CD19+ B cells. Histological studies showed that RP105 is expressed mainly on mature B cells in mantle zones. Germinal center cells are either dull or negative. RP105 is thus a novel human B-cell marker that is preferentially expressed on mature B cells. Moreover, the anti-RP105 MoAb activates B cells, leading to increases in cell size, expression of a costimulatory molecule CD80, and DNA synthesis. The B-cell activation pathway using RP105 is conserved in humans. © 1998 by The American Society of Hematology.

scholarly journals Regulated expression and function of CD11c/CD18 integrin on human B lymphocytes. Relation between attachment to fibrinogen and triggering of proliferation through CD11c/CD18.

1991 ◽  
Vol 174 (6) ◽  
pp. 1313-1322 ◽  
Author(s):  
A A Postigo ◽  
A L Corbí ◽  
F Sánchez-Madrid ◽  
M O de Landázuri
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Phorbol Esters ◽  
De Novo ◽  
Lymphoid Cells ◽  
Cell Surface Expression ◽  
Cytotoxic T Cell ◽  
And Function

CD11c/CD18 (p150,95) is a beta 2 integrin expressed by myeloid, natural killer and certain lymphoid cells such as some cytotoxic T cell clones and B cell malignancies. We have studied the expression and function of CD11c on resting and activated B lymphocytes. Flow cytometry, immunoprecipitation, and mRNA analyses showed that cell activation with phorbol esters or with a variety of stimuli such as Staphylococcus aureus or anti-mu antibodies in combination with cytokines induced de novo CD11c/CD18 cell surface expression on most B cells while CD11b expression was not affected. Functional analysis of CD11c/CD18 on B cells revealed that it plays a dual role. First, CD11c/CD18 is implicated in B cell proliferation, as demonstrated by the ability of several anti-CD11c monoclonal antibodies to trigger comitogenic signals; and second, the newly expressed CD11c/CD18 mediates B cell binding to fibrinogen. Our data conclusively demonstrate the role of CD11c/CD18 on both B cell activation and adhesion processes.

scholarly journals Activation of B lymphocytes by monovalent anti-Lyb-2 antibodies.

1984 ◽  
Vol 159 (6) ◽  
pp. 1796-1801 ◽  
Author(s):  
B Subbarao ◽  
D E Mosier
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Cell Transformation ◽  
Receptor Occupancy ◽  
Cross Linking ◽  
B Cell Activation ◽  
Fab Fragments

Although activation of B lymphocytes by antigen or anti-Ig antibody has been shown to require cross-linking of surface Ig molecules, cross-linking is not necessary for B cell activation by anti-Lyb-2 monoclonal antibody (MAb). Monovalent Fab' fragments of anti-Lyb-2 MAb are as effective as the intact antibody in inducing blast cell transformation of small B cells and B cell proliferation in the apparent absence of T cells and adherent cells. In the presence of factors from T cells, B cells activated by Fab' fragments of anti-Lyb-2 MAb were induced to mature into Ig-secreting cells. Since monovalent Fab' fragments probably cannot induce receptor aggregation, it appears that receptor occupancy is sufficient to induce B cell activation with anti-Lyb-2 MAb.

RP105 Is Associated With MD-1 and Transmits an Activation Signal in Human B Cells

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2815-2822 ◽  
Author(s):  
Yoshihiro Miura ◽  
Rintaro Shimazu ◽  
Kensuke Miyake ◽  
Sachiko Akashi ◽  
Hirotaka Ogata ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
B Cell Activation ◽  
Cell Surface Molecule ◽  
Induced Apoptosis

RP105 was originally discovered as a mouse B-cell surface molecule that transmits an activation signal. The signal leads to resistance against irradiation-induced apoptosis and massive B-cell proliferation. Recently, we found that mouse RP105 is associated with another molecule, MD-1. We have isolated here the human MD-1 cDNA. We show that human MD-1 is also associated with human RP105 and has an important role in cell surface expression of RP105. We also describe a monoclonal antibody (MoAb) that recognizes human RP105. Expression of RP105 is restricted to CD19+ B cells. Histological studies showed that RP105 is expressed mainly on mature B cells in mantle zones. Germinal center cells are either dull or negative. RP105 is thus a novel human B-cell marker that is preferentially expressed on mature B cells. Moreover, the anti-RP105 MoAb activates B cells, leading to increases in cell size, expression of a costimulatory molecule CD80, and DNA synthesis. The B-cell activation pathway using RP105 is conserved in humans. © 1998 by The American Society of Hematology.

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