scholarly journals Antigenic Stimuli do not Influence Thymic B Lymphocytes: A Morphological and Functional Study in Germ-Free and Conventionally Reared Piglets

1998 ◽  
Vol 6 (3-4) ◽  
pp. 171-178 ◽  
Author(s):  
B. Cukrowska ◽  
I. Trebichavský ◽  
P. Rossmann ◽  
Z. Reháková ◽  
J. ŠInkora ◽  
...  
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Cell Subpopulation ◽  
Functional Study ◽  
Germ Free ◽  
Food Antigens ◽  
Before And After ◽  
Embryonic Life ◽  
Thymic Medulla ◽  
Immunohistological Analysis

We have recently reported that thymic B lymphocytes (TBL) are the first B-cell subpopulation undergoing isotype switching to IgG and IgA during embryonic life. The aim of this study is to analyze the influence of antigenic stimulation on TBL location and activity using a germ-free (GF) newborn pig model, in which maternal antibodies and antigens do not affect B-cell development. Immunohistological analysis showed that TBL were disseminated mainly in the thymic medulla. There were no differences in the distribution of TBL, both in GF newborn piglets before and after colonization withEscherichia coliand in older conventionally reared (CONV) piglets. The number of immunoglobulin (Ig)-secreting cells measured by the ELISPOT method was not influenced by microflora and food antigens. IgM-positive cells secreting IgM and CD45RC-positive cells spontaneously producing IgM, IgG, and IgA were detected in newborn thymus.Our findings suggest that TBL differentiation and Ig switching to IgG and IgA-secreting cells is not influenced by external antigens and that the thymic microenviroment plays an important role in this process.

scholarly journals Studies of in vitro activated CD5+ B cells

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 202-208 ◽  
Author(s):  
AS Freedman ◽  
G Freeman ◽  
J Whitman ◽  
J Segil ◽  
J Daley ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Tritiated Thymidine ◽  
Interleukin 1 ◽  
Cell Subpopulation ◽  
Recombinant Interferon ◽  
Barr Virus

Abstract Human B lymphocytes undergo distinct phenotypic changes following activation with antigen and polyclonal mitogens. Increasing interest has focused on the unique subpopulation of B cells that expresses the CD5 antigen. In this study, we examined the signals that induce the expression of CD5 on normal splenic B cells. Only 12-O- tetradecanoylphorbol-13-acetate (TPA) induced CD5 expression on highly purified splenic B cells, whereas anti-immunoglobulin (anti-Ig), Epstein-Barr virus, anti-CD20, recombinant interleukin-1 (rIL-1), rIL- 2, rIL-4, recombinant interferon-gamma (rINF-gamma), and B-cell growth factor all failed to induce CD5 expression. The expression of CD5 was detected on the cell surface by 48 hours and decreased by 96 hours. Dual-fluorochrome analysis demonstrated that the CD5+ B cells coexpressed the B-cell activation antigens B5, IL-2 receptor, and CD23, thereby providing phenotypic evidence that this B-cell subpopulation is activated. In vitro studies of dual-fluorochrome-sorted, TPA-stimulated splenic B cells demonstrated significantly greater tritiated thymidine incorporation and Ig secretion by the CD20+ CD5- cells than by the CD20+ CD5+ subset. These phenotypic and functional studies are consistent with the notion that TPA-induced CD5+ B cells are a subset of in vitro activated B lymphocytes.

scholarly journals Autoantibody-associated cross-reactive idiotype-bearing human B lymphocytes: distribution and characterization, including Ig VH gene and CD5 antigen expression

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1503-1515 ◽  
Author(s):  
G Inghirami ◽  
DR Foitl ◽  
A Sabichi ◽  
BY Zhu ◽  
DM Knowles
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Subset ◽  
Antigen Expression ◽  
Lymphocytic Leukemia ◽  
Cell Subpopulation ◽  
Lymphoid Tissues ◽  
Vh Gene

Abstract Monoclonal antibodies (MoAbs) specific for autoantibody associated cross-reactive idiotypes (CRIs) frequently recognize the Igs of neoplastic B cells in patients with chronic lymphocytic leukemia (CLL) and/or Waldenstrom's macroglobulinemia. Very little is known regarding the normal B cells expressing CRIs (CRI-positive B cells). Using a variety of MoAbs against CRIs we investigated the distribution and topographic localization of CRI-positive B cells in normal adult human lymphoid tissues. We found that CRI-positive B cells represent a significant B-cell subpopulation expressing surface IgM (greater than 90%), IgG (approximately 5%), or IgA (approximately 2%). CRI-positive B cells are homogeneously distributed throughout all lymphoid tissues, accounting for 10% to 15% of all B lymphocytes, with the exception of the thymus, in which they represent the predominant B cell population. Immunophenotypic studies showed (1) that a small subpopulation (3.7% +/- 0.8%) of CRI-positive B cells are activated in vivo, based on CD25 and CD38 antigen expression; and (2) that approximately 50% of CRI-positive B cells express the 67-Kd pan-T-lymphocyte CD5 antigen, suggesting that the CRI-positive B-cell subset and the recently described CD5-positive B-cell subset are closely related. This hypothesis is supported by the fact that CRI-positive B cells produce oligo or polyreactive Igs, which are a characteristic feature of CD5-positive B cells, and also by the fact that both B-cell subpopulations appear to use similar and restricted Ig VH gene family members.

scholarly journals Studies of in vitro activated CD5+ B cells

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 202-208
Author(s):  
AS Freedman ◽  
G Freeman ◽  
J Whitman ◽  
J Segil ◽  
J Daley ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Tritiated Thymidine ◽  
Interleukin 1 ◽  
Cell Subpopulation ◽  
Recombinant Interferon ◽  
Barr Virus

Human B lymphocytes undergo distinct phenotypic changes following activation with antigen and polyclonal mitogens. Increasing interest has focused on the unique subpopulation of B cells that expresses the CD5 antigen. In this study, we examined the signals that induce the expression of CD5 on normal splenic B cells. Only 12-O- tetradecanoylphorbol-13-acetate (TPA) induced CD5 expression on highly purified splenic B cells, whereas anti-immunoglobulin (anti-Ig), Epstein-Barr virus, anti-CD20, recombinant interleukin-1 (rIL-1), rIL- 2, rIL-4, recombinant interferon-gamma (rINF-gamma), and B-cell growth factor all failed to induce CD5 expression. The expression of CD5 was detected on the cell surface by 48 hours and decreased by 96 hours. Dual-fluorochrome analysis demonstrated that the CD5+ B cells coexpressed the B-cell activation antigens B5, IL-2 receptor, and CD23, thereby providing phenotypic evidence that this B-cell subpopulation is activated. In vitro studies of dual-fluorochrome-sorted, TPA-stimulated splenic B cells demonstrated significantly greater tritiated thymidine incorporation and Ig secretion by the CD20+ CD5- cells than by the CD20+ CD5+ subset. These phenotypic and functional studies are consistent with the notion that TPA-induced CD5+ B cells are a subset of in vitro activated B lymphocytes.

scholarly journals The immunomodulatory function of human amniotic fluid stromal cells on B lymphocytes

2018 ◽  
Vol 1 (1) ◽  
pp. 122-133
Author(s):  
Qun Xue ◽  
Zhou Yin ◽  
Nagam Varshithreddy ◽  
Han-si Liang ◽  
Ming-yuan Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Amniotic Fluid ◽  
B Cell ◽  
B Lymphocytes ◽  
Stromal Cells ◽  
Cell Activity ◽  
Costimulatory Molecules ◽  
Cell Subpopulation ◽  
Human Amniotic Fluid ◽  
Immunomodulatory Function

Current treatments for B cell-mediated disease are mainly based on global B cell depletion, thereby eliminating pathogenic B cells as well as Breg subsets. A more refined modulation of B cell activity could prove beneficial for patient treatment.Objective:To investigate the immunomodulatory function of human amniotic fluid stromal cells (hAFSCs) on different subpopulation of B lymphocytes.Methods:hAFSCs were isolated and cultured and identified by characteristic phenotypic markers. After coculture of B lymphocytes with hAFSCs, the activation, proliferation, differentiation, as well as apoptosis, cell cycle, and expression of the inhibitory costimulatory molecules B7H1, B7H3, and B7H4 of B lymphocytes were examined in vitro.Results:Coculture with hAFSCs significantly decreased the expression of CD80/CD86, Ki-67 and CFSE expression, on activated B lymphocytes. These might be due to the inhibition of B lymphocyte apoptosis and cell cycle arrest. In activated B lymphocytes, coculture with hAFSCs resulted in a reduced proportion of memory B and plasma cells, reduced amounts of immunoglobulins. hAFSCs could balance the B1 to B2 cell subpopulation ratio. hAFSCs could inhibit the expression of the negative co-inhibitory molecule B7H4 and PD-L1 on the activated B lymphocytes.Conclusion:hAFSCs could inhibit B cell activation, proliferation, and subpopulation differentiation. These might be due to their affect on B cell apoptosis, cell cycle and the expression of costimulatory molecules of human B lymphocytes. Our experiment provided the evidence for hAFSCs as ideal seed cells with therapeutic potential for treating humoral immunity disorders, which were mainly mediated by B lymphocytes.

scholarly journals Autoantibody-associated cross-reactive idiotype-bearing human B lymphocytes: distribution and characterization, including Ig VH gene and CD5 antigen expression

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1503-1515
Author(s):  
G Inghirami ◽  
DR Foitl ◽  
A Sabichi ◽  
BY Zhu ◽  
DM Knowles
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Subset ◽  
Antigen Expression ◽  
Lymphocytic Leukemia ◽  
Cell Subpopulation ◽  
Lymphoid Tissues ◽  
Vh Gene

Monoclonal antibodies (MoAbs) specific for autoantibody associated cross-reactive idiotypes (CRIs) frequently recognize the Igs of neoplastic B cells in patients with chronic lymphocytic leukemia (CLL) and/or Waldenstrom's macroglobulinemia. Very little is known regarding the normal B cells expressing CRIs (CRI-positive B cells). Using a variety of MoAbs against CRIs we investigated the distribution and topographic localization of CRI-positive B cells in normal adult human lymphoid tissues. We found that CRI-positive B cells represent a significant B-cell subpopulation expressing surface IgM (greater than 90%), IgG (approximately 5%), or IgA (approximately 2%). CRI-positive B cells are homogeneously distributed throughout all lymphoid tissues, accounting for 10% to 15% of all B lymphocytes, with the exception of the thymus, in which they represent the predominant B cell population. Immunophenotypic studies showed (1) that a small subpopulation (3.7% +/- 0.8%) of CRI-positive B cells are activated in vivo, based on CD25 and CD38 antigen expression; and (2) that approximately 50% of CRI-positive B cells express the 67-Kd pan-T-lymphocyte CD5 antigen, suggesting that the CRI-positive B-cell subset and the recently described CD5-positive B-cell subset are closely related. This hypothesis is supported by the fact that CRI-positive B cells produce oligo or polyreactive Igs, which are a characteristic feature of CD5-positive B cells, and also by the fact that both B-cell subpopulations appear to use similar and restricted Ig VH gene family members.

scholarly journals Antiviral Treatment Down-Regulates Peripheral B-Cell CD81 Expression and CD5 Expansion in Chronic Hepatitis C Virus Infection

2003 ◽  
Vol 77 (19) ◽  
pp. 10432-10436 ◽  
Author(s):  
Eli Zuckerman ◽  
Aharon Kessel ◽  
Gleb Slobodin ◽  
Edmond Sabo ◽  
Daniel Yeshurun ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cells ◽  
B Cell ◽  
Antiviral Therapy ◽  
Antiviral Treatment ◽  
Cell Subpopulation ◽  
Hcv Rna ◽  
Healthy Controls ◽  
Before And After

ABSTRACT Hepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation. Recently, CD81 was identified as an HCV receptor on B lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. It has recently been shown that peripheral B-cell CD81 overexpression and CD5+ subpopulation expansion correlate with HCV viral load and are associated with the development of HCV-related autoimmunity. In the present study, we assessed the effects of combination antiviral therapy (alfa interferon and ribavirin) on peripheral B-cell CD81 expression and CD5 expansion and the presence of autoimmune markers. Peripheral B-cell CD5 expression and the mean fluorescence intensity of CD81 were assessed by flow cytometry before and after treatment in 15 HCV-infected patients, in 10 untreated patients, and in 25 healthy controls. A significant posttreatment decrease in peripheral B-cell CD81 expression and disappearance of CD5+ B-cell expansion were observed in all nine patients in whom a complete and sustained virological response was achieved (P < 0.01) (comparable to those for healthy controls). The decrease in CD81 overexpression and CD5 expansion in these patients was associated with a decrease and/or disappearance of autoimmune markers. In contrast, in nonresponders overexpression of CD81 and expansion of the CD5+ B-cell subpopulation were not significantly changed and were comparable to those for untreated patients. In conclusion, antiviral therapy down-regulates peripheral B-cell CD81 expression and the CD5+ population, either directly or by its effect on HCV RNA load. The overexpression of CD81 and the expansion of the population of CD5+ peripheral B cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation.

Subpopulations of B lymphocytes in germinal centers, II. A germinal center B cell subpopulation expresses sIgD and CD23

1989 ◽  
Vol 21 (3) ◽  
pp. 201-208 ◽  
Author(s):  
Moon H. Nahm ◽  
Peter A. Takes ◽  
Mary Beth Bowen ◽  
Kimberly A. Macke
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Germinal Center ◽  
Germinal Centers ◽  
Cell Subpopulation ◽  
Germinal Center B Cell

scholarly journals Monoclonal anti-light chain idiotype as a tumor-specific probe for human neoplastic B lymphocytes

Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 919-923 ◽  
Author(s):  
M Wrightham ◽  
AL Tutt ◽  
MJ Glennie ◽  
TJ Hamblin ◽  
GT Stevenson ◽  
...  
Keyword(s):  
B Cell ◽  
Tumor Cells ◽  
B Lymphocytes ◽  
Light Chain ◽  
Normal Serum ◽  
Lymphocytic Leukemia ◽  
Light Chains ◽  
Specific Probe ◽  
Tonsillar Cells ◽  
Binding Curves

Abstract Tumor cells from patients with B cell neoplasms often secrete small amounts of free monoclonal light chains that can be found in the urine. Such tumor-derived light chains of the lambda type from a patient with typical chronic lymphocytic leukemia have been used to raise mouse monoclonal antibodies (MoAbs). A hybridoma-secreting antibody that recognized the idiotypic lambda chain but not normal lambda chains by a preliminary screen but which also reacted with idiotypic IgM from the patient's tumor cells was selected. This MoAb in fact recognized 1 in 20 X 10(3) molecules of pooled normal lambda chains, thus establishing its specificity for a private idiotypic determinant. It failed to give a detectable reaction with normal IgM, normal serum, or a panel of IgM paraproteins. The antibody bound to the patient's neoplastic B cells but not to normal tonsillar cells. The site of binding of the antibody to idiotypic IgM is clearly separate from that of another MoAb specific for idiotypic determinants on heavy plus light chains, since the two showed additive binding curves. The determinant also appeared to be less available in dimeric lambda chains than in monomeric lambda chains or in idiotypic IgM. Antibodies to idiotypic determinants on light chains show some technical advantages and should be useful for monitoring and possibly treating B cell tumors, either alone or together with the more conventional anti-idiotypic antibodies that usually recognize the heavy and light chain combination.

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 Metabolic Swifts Govern Normal and Malignant B Cell Lymphopoiesis

2021 ◽  
Vol 22 (15) ◽  
pp. 8269
Author(s):  
Aikaterini Poulaki ◽  
Stavroula Giannouli
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Control Program ◽  
Memory B Cells ◽  
Immunologic Memory ◽  
Human Immune System ◽  
B Cell Malignancies ◽  
Stringent Control ◽  
Human Immune ◽  
New Research

B lymphocytes are an indispensable part of the human immune system. They are the effective mediators of adaptive immunity and memory. To accomplish specificity against an antigen, and to establish the related immunologic memory, B cells differentiate through a complicated and strenuous training program that is characterized by multiple drastic genomic modifications. In order to avoid malignant transformation, these events are tightly regulated by multiple checkpoints, the vast majority of them involving bioenergetic alterations. Despite this stringent control program, B cell malignancies are amongst the top ten most common worldwide. In an effort to better understand malignant pathobiology, in this review, we summarize the metabolic swifts that govern normal B cell lymphopoiesis. We also review the existent knowledge regarding malignant metabolism as a means to unravel new research goals and/or therapeutic targets.

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