scholarly journals Cxcr4 desensitization is an essential regulatory mechanism controlling the extra-follicular B cell response

2019 ◽  
Author(s):  
Nagham Alouche ◽  
Amélie Bonaud ◽  
Vincent Rondeau ◽  
Julie Nguyen ◽  
Etienne Cricks ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
B Lymphocyte ◽  
Regulatory Mechanism ◽  
B Cell Activation ◽  
Whim Syndrome ◽  
C Terminus ◽  
Signaling Axis ◽  
Chemokine Cxcl12 ◽  
Follicular Response

AbstractThe signaling axis formed by the chemokine CXCL12 and its receptor CXCR4 plays an important role in B cell development and activation and is finely regulated by a process termed desensitization. Mutations leading to a truncation of the C-terminus tail of CXCR4 and thus to a defective desensitization have been reported in two diseases, a rare immunodeficiency called the WHIM syndrome and a B cell plasmacytoma called Waldenstrom’s Macroglobulinemia (WM). How CXCR4 desensitization may impact B cell activation in the context of a T-independent extra-follicular response is still unknown. Here using a unique mouse model bearing an orthologous gain of function mutation of Cxcr4 we report that Cxcr4 desensitization is an essential gatekeeper controlling B lymphocyte entry into cycle, plasma cell differentiation, migration and maturation upon Myd88-dependent signaling. Altogether, our results support an essential role for Cxcr4 desensitization in limiting the depth and width of the B cell extra-follicular response and PC development.

Expression of XBP1s in B lymphocytes is critical for pristane-induced lupus nephritis in mice

2020 ◽  
Vol 318 (5) ◽  
pp. F1258-F1270 ◽  
Author(s):  
Li Xiang ◽  
An Liu ◽  
Guoshuang Xu
Keyword(s):  
B Cells ◽  
Lupus Nephritis ◽  
Mouse Model ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
B Lymphocyte ◽  
B Cell Activation ◽  
Protein Levels ◽  
Almost All

B lymphocyte hyperactivity plays a pathogenic role in systemic lupus erythematosus (SLE), and spliced X box-binding protein 1 (XBP1s) has been implicated in B cell maturation and differentiation. We hypothesized that blockade of the XBP1s pathway inhibits the B cell hyperactivity underlying SLE and lupus nephritis (LN) development. In the present study, we systematically evaluated the changes in B cell activation induced by the Xbp1 splicing inhibitor STF083010 in a pristane-induced lupus mouse model. The lupus mouse model was successfully established, as indicated by the presence of LN with markedly increased urine protein levels, renal deposition of Ig, and mesangial cell proliferation. In lupus mice, B cell hyperactivity was confirmed by increased CD40 and B cell-activating factor levels. B cell activation and plasma cell overproduction were determined by increases in CD40-positive and CD138-positive cells in the spleens of lupus mice by flow cytometry and further confirmed by CD45R and Ig light chain staining in the splenic tissues of lupus mice. mRNA and protein expression of XBP1s in B cells was assessed by real-time PCR, Western blot analysis, and immunofluorescence analysis and was increased in lupus mice. In addition, almost all changes were reversed by STF083010 treatment. However, the expression of XBP1s in the kidneys did not change when mice were exposed to pristane and STF083010. Taken together, these findings suggest that expression of XBP1s in B cells plays key roles in SLE and LN development. Blockade of the XBP1s pathway may be a potential strategy for SLE and LN treatment.

CD22 antigen: biosynthesis, glycosyiation and surface expression of a B lymphocyte protein involved in B cell activation and adhesion

1991 ◽  
Vol 3 (7) ◽  
pp. 623-633 ◽  
Author(s):  
Reinhard Schwartz-Albiez ◽  
Bernd Dörken ◽  
Davidv A. Monner ◽  
Gerhard Moldenhauer
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
B Lymphocyte ◽  
Surface Expression ◽  
B Cell Activation

scholarly journals Constitutive BR3 receptor signaling in diffuse, large B-cell lymphomas stabilizes nuclear factor-κB–inducing kinase while activating both canonical and alternative nuclear factor-κB pathways

Blood ◽  
2011 ◽  
Vol 117 (1) ◽  
pp. 200-210 ◽  
Author(s):  
Lan V. Pham ◽  
Lingchen Fu ◽  
Archito T. Tamayo ◽  
Carlos Bueso-Ramos ◽  
Elias Drakos ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
B Lymphocyte ◽  
Tumor Necrosis Factor Receptor ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Genetically Engineered ◽  
Nuclear Factor ◽  
B Cell Activation ◽  
Large B Cell

Abstract Aberrant nuclear factor κB (NF-κB) signaling has been found to be of particular importance in diffuse, large B-cell lymphoma (DLBCL) cell survival and proliferation. Although the canonical NF-κB signaling pathway has been studied in some detail, activation of the alternative NF-κB pathway in DLBCL is not well characterized. Important insights into the regulation of the alternative NF-κB pathway in B lymphocytes has recently revealed the regulatory importance of the survival kinase NIK (NF-κB–inducing kinase) in genetically engineered murine models. Our studies demonstrate that both the canonical and alternative NF-κB pathways are constitutively activated in DLBCL. We also demonstrate that NIK kinase aberrantly accumulates in DLBCL cells due to constitutive activation of B-cell activation factor (BAFF)–R (BR3) through interaction with autochthonous B-lymphocyte stimulator (BLyS) ligand in DLBCL cells. Activation of BR3 in DLBCL induces recruitment and degradation of tumor necrosis factor receptor-associated factor 3, which results in NIK kinase accumulation, IκBα phosphorylation, and NF-κB p100 processing, thereby resulting in continuous activation of both NF-κB pathways in DLBCL cells, leading to autonomous lymphoma cell growth and survival. These results further elucidate mechanisms involved in abnormal NF-κB activation in DLBCL, and should contribute to better future therapeutic approaches for patients with DLBCL.

scholarly journals Crosslinkage of B lymphocyte surface immunoglobulin by anti-Ig or antigen induces prolonged oscillation of intracellular ionized calcium.

1987 ◽  
Vol 166 (2) ◽  
pp. 601-606 ◽  
Author(s):  
H A Wilson ◽  
D Greenblatt ◽  
M Poenie ◽  
F D Finkelman ◽  
R Y Tsien
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
B Lymphocyte ◽  
Accessory Cell ◽  
Base Line ◽  
B Cell Differentiation ◽  
B Cell Activation ◽  
Technical Approach ◽  
Indicator Dyes

Our results indicate that B lymphocytes stimulated with anti-Ig or antigen exhibit repetitive [Ca2+]i transients which persist for hours. The magnitude of these transients favors an important and ongoing role for [Ca2+]i elevation in antigen driven B cell activation. Repetitive Ca2+ transients may prove to be a prevalent mechanism of Ca2+ signaling. In preliminary experiments (with L. E. Samelson and R. D. Klausner), we have observed Ca2+ transients in cloned T cells stimulated with antigen. Woods et al. have described repetitive free Ca2+ transients in hepatocytes stimulated with extracellular ligands promoting glycogenolysis, and suggest that the intervals of base-line [Ca2+]i levels explain the absence of mitochondrial overload in chronically stimulated cells. These considerations apply equally to B lymphocytes and recommend caution in delineating the range of Ca2+-mediated functions by prolonged coculture of cells with Ca2+ ionophores. Our experiments were done in a simple recording chamber with one cell type. No cell interactions were observed. Given the variety of indicator dyes now available, the technical approach we present, augmented by a more sophisticated recording chamber, is a potentially powerful tool for examining the intrinsic, and T- or accessory cell-dependent, physiology of B cell differentiation.

scholarly journals Regulation of B-lymphocyte clonal proliferation by stimulatory and inhibitory macrophage-derived factors

1977 ◽  
Vol 146 (5) ◽  
pp. 1420-1435 ◽  
Author(s):  
JI Kurland ◽  
PW Kincade ◽  
MAS Moore
Keyword(s):  
Lymph Node ◽  
B Cell ◽  
Colony Formation ◽  
Cell Activation ◽  
B Lymphocyte ◽  
Optimal Number ◽  
B Cell Activation ◽  
Agar Culture ◽  
Sheep Erythrocytes ◽  
Clonal Proliferation

A functional subpopulation of murine B lymphocytes proliferate in semisolid agar culture in the presence of 2-mercaptoethanol to form colonies. The effects of diffusible macrophage-derived factors on this focal proliferation was investigated using a two-layer culture system which prevented macrophage-lymphocyte contact and permitted B-cell activation to be critically assessed under conditions of extremely low cell densities. Adherent peritoneal macrophages incorporated within underlayers of spleen or lymph node cell cultures potentiated both the number and size of developing B-cell colonies. These effects were most striking when low numbers of spleen or lymph node cells, or macrophage- depleted lymphoid cell suspensions were used. Thus, macrophage-depleted lymph node ceils gave rise to virtually no colonies, but colony-forming ability was restored by the presence of an optimal number of macrophages. When the number of macrophages exceeded that required for optimal stimulation, colony formation was suppressed; an effect which was largely prevented by indomethacin, an inhibitor of prostaglandin synthesis. Under these conditions, stimulation and inhibition of B-cell activation by macrophages could be dissociated, indicating that each signal is selectively controlled by individual molecules elaborated by the macrophage. With an appropriate number of macrophages required for B-cell activation, and sufficient indomethacin to inhibit the accumulation of macrophage-derived prostaglandin, B-lymphocyte clonal proliferation was a linear function of the number of B cells placed in culture. In the absence of macrophages, B-cell colony formation was potentiated by both lipopolysaccharide and intact sheep erythrocytes through a mechanism different from that of the macrophage-derived stimulatory factor. In addition to their direct stimulatory effect on B-cell proliferation, lipopolysaccharide and sheep erythrocytes were each capable of modulating the production and/or release of B-cell stimulatory and inhibitory factors by the macrophage. Parallel studies of conventional mitogen- stimulated lymphocyte cultures did not show a requirement for macrophages and confirm that the semisolid assay is uniquely suited to studies on the regulatory role of the macrophage in B-cell activation.

B-Cell Activation by Helper T-Cell Membranes

1994 ◽  
Vol 14 (3-4) ◽  
pp. 221-238 ◽  
Author(s):  
Marilyn R. Kehry ◽  
Philip D. Hodgkin
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Membranes ◽  
Cell Activation ◽  
B Cell Activation ◽  
Helper T Cell
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