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.

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 Transcriptional program of memory B cell activation, broadly binding anti-influenza antibodies, and bystander activation after vaccination revealed by single-cell transcriptomics

2019 ◽  
Author(s):  
Felix Horns ◽  
Cornelia L. Dekker ◽  
Stephen R. Quake
Keyword(s):  
Influenza Vaccination ◽  
B Cell ◽  
Single Cell ◽  
Cell Activation ◽  
Transcriptional Profiling ◽  
Affinity Maturation ◽  
B Cell Activation ◽  
Cell Repertoire ◽  
Memory B Cell ◽  
Clonal Proliferation

AbstractAntibody memory protects humans from many diseases. Protective antibody memory responses require activation of transcriptional programs, cell proliferation, and production of antigen-specific antibodies, but how these aspects of the response are coordinated is poorly understood. We profiled the molecular and cellular features of the antibody response to influenza vaccination by integrating single-cell transcriptomics, longitudinal antibody repertoire sequencing, and antibody binding measurements. Single-cell transcriptional profiling revealed a program of memory B cell activation characterized by CD11c and T-bet expression associated with clonal expansion and differentiation toward effector function. Vaccination elicited an antibody clone which rapidly acquired broad high-affinity hemagglutinin binding during affinity maturation. Unexpectedly, many antibody clones elicited by vaccination do not bind vaccine, demonstrating non-specific activation of bystander antibodies by influenza vaccination. These results offer insight into how molecular recognition, transcriptional programs, and clonal proliferation are coordinated in the human B cell repertoire during memory recall.

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.

scholarly journals Enhanced Follicular Dendritic Cell-B Cell Interaction in HIV and SIV Infections and its Potential Role in Polyclonal B Cell Activation

1998 ◽  
Vol 6 (1-2) ◽  
pp. 61-70 ◽  
Author(s):  
Yvonne J. Rosenberg ◽  
Mark. G. Lewis ◽  
Marie H. Kosco-Vilbois
Keyword(s):  
Lymph Node ◽  
Dendritic Cell ◽  
B Cell ◽  
Cell Activation ◽  
Follicular Dendritic Cell ◽  
Cell Interaction ◽  
Germinal Centers ◽  
B Cell Activation ◽  
Immunodeficiency Virus ◽  
Follicular Dendritic

Human immunodeficiency virus (HIV) infections have been characterized by both polyclonal Bcell activation and enhanced responsiveness to B-cell growth factors on one hand and the loss of specific antibody (Ab) responses and refractoriness to the normal signals for B-cell activation on the other. Histopathological studies of lymph node from HIV- and simian immunodeficiency virus (SIV)-infected individuals have indicated initial follicular hyperplasia and the appearance of large irregular germinal centers that undergo progressive involution concomitant with follicular dendritic-cell (FDC) disruption. During this process, follicular dendritic-cell -enriched lymph-node-cell cultures exhibit increased ability to induce cluster formation (“in vitrogerminal centers”), lymphocyte proliferation and antibody production compared to uninfected controls. This paper discusses how enhanced FDC-B-cell interaction within SIV-infected germinal centers may result in a reduced ability to select high-affinity B cells and alter the dynamics of antibodyproducing- cell and memory-cell generation resulting in the observed hyperactivity.

scholarly journals COMPLEMENT-DEPENDENT B-CELL ACTIVATION BY COBRA VENOM FACTOR AND OTHER MITOGENS?

1974 ◽  
Vol 139 (2) ◽  
pp. 337-354 ◽  
Author(s):  
Peter Dukor ◽  
Gebhard Schumann ◽  
Roland H. Gisler ◽  
Manfred Dierich ◽  
Wolfgang König ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Cultures ◽  
Antibody Formation ◽  
Cell Activation ◽  
B Cell Activation

It has been proposed that two distinct signals are required for the triggering of the precursors of antibody-forming bone marrow-derived cells (B cells): (a) the binding of antigen or of a mitogen to the corresponding receptor sites on B-cell membranes and (b) the interaction of activated C3 with the C3 receptor of B lymphocytes. There is growing evidence that B-cell mitogens and T (thymus-derived cell)-independent antigens are capable of activating the alternate pathway of the complement system (bypass). Therefore, the effect of another potent bypass inducer was investigated with regard to B-cell activation and the role of C3. Purified, pyrogen-free cobra venom factor was mitogenic for both T and B lymphocytes (cortisone-resistant mouse thymus cells and lymph node lymphocytes from congenitally athymic mice). Venom factor could substitute for T cells by restoring the potential of antibody formation to sheep red blood cells in mouse B-cell cultures supplemented with macrophages or 2-mercaptoethanol. Venom factor may be capable of conferring activated C3 to the C3 receptor of B lymphocytes: preincubation of lymphoid cells with homologous serum or plasma, 10 mM EDTA, and sepharose-coupled venom factor converted with serum to an enzyme active against C3, inhibited their capacity to subsequently form rosettes with sheep erythrocytes sensitized with amboceptor and C5-deficient mouse complement. In the absence of EDTA, preincubation of freshly prepared B-cell suspensions with C3-sufficient homologous serum also blocked their subsequent interaction with complement-sensitized erythrocytes and at the same time rendered them reactive to an otherwise T-cell-specific mitogen. Moreover, mitogen induced B-cell proliferation in lymph node (but not in spleen) cell cultures, appeared to depend on the availability of exogenous C3: zymosan-absorbed fetal bovine serum (only 8.3% site-forming units remaining) supported T-cell activation by phytohemagglutinin, concanavalin A, and venom factor, but failed to sustain B-cell stimulation by pokeweed mitogen, lipopolysaccharide, and venom factor. T-cell-dependent antibody formation in composite cultures containing T cells or T-cell-substituting B-cell mitogens, B cells, and macrophages, always required the presence of C3-sufficient serum.

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