Heterogeneous subsets of B-lineage regulatory cells (Breg cells)

2019 ◽  
Vol 32 (3) ◽  
pp. 155-162 ◽  
Author(s):  
Yoshihiro Baba ◽  
Yuichi Saito ◽  
Yasuaki Kotetsu
Keyword(s):  
B Cells ◽  
Cellular Component ◽  
Regulatory Cells ◽  
Regulatory Activity ◽  
Environmental Signals ◽  
Inhibitory Function ◽  
Regulatory Ability ◽  
B Lineage ◽  
B Cell Subsets ◽  
And Function

Abstract B cells represent a key cellular component of humoral immunity. Besides antigen presentation and antibody production, B cells also play a role in immune regulation and induction of tolerance through several mechanisms. Our understanding of B-lineage cells with regulatory ability has been revolutionized by the delineation of heterogeneous subsets of these cells. Specific environmental signals may further determine the polarization and function of B-lineage regulatory cells. With the availability of new genetic, molecular and pharmacological tools, considerable advances have been made toward our understanding of the surface phenotype, developmental processes and functions of these cells. These exciting discoveries, some of which are still controversial, also raise many new questions, which makes the inhibitory function of B cells a rapidly growing field in immunopathology. Here we review highlights of the regulatory activity of B cells and the recent advances in the function and phenotype of these B-cell subsets in healthy and diseased states.

The development of functional B lymphocytes in conditional PU.1 knock-out mice

Blood ◽  
2005 ◽  
Vol 106 (6) ◽  
pp. 2083-2090 ◽  
Author(s):  
Matthew Polli ◽  
Aleksandar Dakic ◽  
Amanda Light ◽  
Li Wu ◽  
David M. Tarlinton ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Fetal Liver ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
Knock Out ◽  
B Lineage ◽  
And Function

Abstract An abundance of research has entrenched the view that the Ets domain containing transcription factor PU.1 is fundamental to the development and function of B lymphocytes. In this study, we have made use of a conditional PU.1 allele to test this notion. Complete deletion of PU.1 resulted in the loss of B cells and all other lineage-positive cells in the fetal liver and death between E18.5 and birth; however, specific deletion of PU.1 in the B lineage had no effect on B-cell development. Furthermore, deletion of PU.1 in B cells did not compromise their ability to establish and maintain an immune response. An increased level of apoptosis was observed in vitro upon B-cell receptor (BCR) cross-linking; however, this was partially rescued by interleukin-4 (IL-4). These findings suggest that PU.1 is not essential for the development of functional B lymphocytes beyond the pre-B stage. (Blood. 2005;106:2083-2090)

scholarly journals Multiple Myeloma Includes Phenotypically Defined Subsets of Clonotypic CD20+ B Cells that Persist during Treatment with Rituximab

2008 ◽  
Vol 2 ◽  
pp. CMO.S615 ◽  
Author(s):  
Linda M. Pilarski ◽  
Eva Baigorri ◽  
Michael J. Mant ◽  
Patrick M. Pilarski ◽  
Penelope Adamson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
B Cell ◽  
Plasma Cells ◽  
Cell Subset ◽  
Light Scatter ◽  
Cell Compartments ◽  
B Lineage ◽  
B Cell Subsets ◽  
Anti Cd20

Potential progenitor B cell compartments in multiple myeloma (MM) are clinically important. MM B cells and some circulating MM plasma cells express CD20, predicting their clearance by treatment with anti-CD20. Here we describe two types of clonotypic CD20+ B cell in peripheral blood of myeloma patients, identified by their expression of CD19 and CD20 epitopes, their expression of CD45RA and their light scatter properties. Thus, the circulating component of the MM clone includes at least two distinct CD19+ CD20+ B cell compartments, as well as CD138+CD20+ plasma cells. To determine whether either or both B cell subsets and the CD20+ plasma cell subset were depleted by anti-CD20 therapy, they were evaluated before, during and after treatment of patients with rituximab (anti-CD20), followed by quantifying B cell subsets over a 5 month period during and after treatment. Overall, all three types of circulating B lineage cells persist despite treatment with rituximab. The inability of rituximab to prolong survival in MM may result from this failure to deplete CD20+ B and plasma cells in MM.

B Cell Depletion Reduces the Number and Function of T- Regulatory Cells and Enhances the Anti Tumor response

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3668-3668
Author(s):  
Tamar Tadmor ◽  
Yu Zhang ◽  
Robert Dunn ◽  
Seung-uon Shin ◽  
Hyung-Mee Cho ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Growth ◽  
B Cell ◽  
T Regulatory Cells ◽  
Tumor Response ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Regulatory Cells ◽  
Tumor Bearing ◽  
And Function

Abstract Abstract 3668 Poster Board III-604 Increasing evidence suggests that B lymphocytes play a central role in inhibiting the immune response against certain tumors, but the underlying mechanisms by which B cells facilitate tumor growth are still poorly understood. In this study, we investigated how the presence or absence of B cells affects expansion and function of T- regulatory cells (‘Tregs’) in a murine tumor model (EMT-6). We compared tumor growth, and the number and function of T- regs cells in wild type immune competent mice ( ICM), B cell deficient mice ( BCDM) and /or in BALB-C mice following B- cell depletion induced by injection of anti murine CD20 antibodies (mCD20 Ab, 18B12, mouse IgG1,k, Biogen-IDEC) Mice were either tumor-naïve or implanted with EMT6 mammary adenocarcinoma cells. Absence of B cells as in BCDM completely inhibited tumor growth in the majority of mice, while B cell depletion in normal mice substantially slowed the growth of EMT-6 tumors compared to wild type mice (ICM). Substantial T regs expansion, as defined by CD4+/CD25+/FOXP3+ cells, was evident on day 26 post tumor inoculation in EMT-6 tumor bearing ICM in comparison to the non- tumor bearing mice ( 15.2 +/− 1.2. % and 11.9 +/− 1.1% respectively), isolated from spleen as compared to naïve or tumor bearing BCDM (10.1+/− 0.2% and 10.8+/− 1.2%) The percentage and absolute number of T-regs in the spleen, tumor draining lymph nodes and tumor bed were significantly reduced in the BCDM and/or B cell depleted ICM compared to tumor bearing ICM (10%+/−0.8, 13.9+/− 1.23% and 17+/− 1.3% respectively p<0.01. data from single cell suspensions isolated from spleens on day 20 post tumor inoculation). Similar effects of B cell depletion on the numbers of T-regs were observed in the setting of pre-established EMT6 mammary tumors. In contrast to tumor bearing mice, differences in T-reg number and function were minimal in tumor free B cell deficient or in B cell depleted naïve mice compared to ICM. T-reg function, measured by suppression assay and proliferation assays, was also markedly reduced in tumor bearing BCDM compared to ICM. Combining B cell and T-reg depletion using i.p. injection of anti CD 25 antibody (PC61 or PBS) resulted in similar rates of tumor regression in B cell depleted mice as were seen in BCDM suggesting that the combination of B cells depletion and further depletion of Tregs augmented anti-tumor response. In conclusion, our studies indicate that B cell depletion may play a useful role in augmenting the T cell anti-tumor response, in part due to their effects on T-regulatory cell biology. Disclosures: Dunn: Biogen IDEC: Employment.

B regulatory cells are increased in hypercholesterolaemic mice and protect from lesion development via IL-10

2015 ◽  
Vol 114 (10) ◽  
pp. 835-847 ◽  
Author(s):  
Paul Blair ◽  
Christoph Leib ◽  
Michael Goddard ◽  
Elizabeth Rosser ◽  
Inhye Park ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Vascular Disease ◽  
Adoptive Transfer ◽  
Lesion Size ◽  
Neointima Formation ◽  
Regulatory Cells ◽  
Lesion Development ◽  
B Regulatory Cells ◽  
B Cell Subsets

SummaryWhilst innate B1-B cells are atheroprotective, adaptive B2-B cells are considered pro-atherogenic. Different subsets of B regulatory cells (Breg) have been described. In experimental arthritis and lupus-like disease, Breg are contained within the CD21hiCD23hiCD24hi B cell pool. The existence and role of Breg in vascular disease is not known. We sought to investigate the existence, identity and location of Breg in vascular disease. The representation of B2-B cell subsets in the spleens and lymph nodes (LNs) of Apolipoprotein E-/- (ApoE-/-) mice compared to controls was characterised by flow cytometry. Additionally, we utilised a model of neointima formation based on the placement of a perivascular collar around the carotid artery in ApoE-/- mice to ascertain whether B cells and B cell subsets confer protection against lesion development. Adoptive transfer of B cells was performed from wild type or genetically modified mice. We showed that CD21hiCD23hiCD24hi B cells are unexpectedly increased in the draining LNs of ApoE-/- mice. Adoptive transfer of LN-derived B2-B cells or purified CD21hiCD23hiCD24hi B cells to syngeneic mice reduced lesion size and inflammation without changing serum cholesterol levels. Follicular B2-B cells did not confer protection. IL-10 blockade or transfer of IL10-deficient B cells prevented LN-derived B cell-mediated protection. This is the first identification of a specific LN-derived B2-Breg subset that confers IL-10 mediated protection from neointima formation. This may open the way for immune modulatory approaches in cardiovascular disease.

scholarly journals Sustained correction of B-cell development and function in a murine model of X-linked agammaglobulinemia (XLA) using retroviral-mediated gene transfer

Blood ◽  
2004 ◽  
Vol 104 (5) ◽  
pp. 1281-1290 ◽  
Author(s):  
Phyllis W. Yu ◽  
Ruby S. Tabuchi ◽  
Roberta M. Kato ◽  
Alexander Astrakhan ◽  
Stephanie Humblet-Baron ◽  
...  
Keyword(s):  
Stem Cells ◽  
B Cells ◽  
Gene Transfer ◽  
B Cell ◽  
Cell Development ◽  
B Cell Development ◽  
Serum Immunoglobulin ◽  
Hematopoietic Stem ◽  
B Lineage ◽  
And Function

Abstract X-linked agammaglobulinemia (XLA) is a human immunodeficiency caused by mutations in Bruton tyrosine kinase (Btk) and characterized by an arrest in early B-cell development, near absence of serum immunoglobulin, and recurrent bacterial infections. Using Btk- and Tec-deficient mice (BtkTec–/–) as a model for XLA, we determined if Btk gene therapy could correct this disorder. Bone marrow (BM) from 5-fluorouracil (5FU)–treated BtkTec–/– mice was transduced with a retroviral vector expressing human Btk and transplanted into BtkTec–/– recipients. Mice engrafted with transduced hematopoietic cells exhibited rescue of both primary and peripheral B-lineage development, recovery of peritoneal B1 B cells, and correction of serum immunoglobulin M (IgM) and IgG3 levels. Gene transfer also restored T-independent type II immune responses, and B-cell antigen receptor (BCR) proliferative responses. B-cell progenitors derived from Btk-transduced stem cells exhibited higher levels of Btk expression than non-B cells; and marking studies demonstrated a selective advantage for Btk-transduced B-lineage cells. BM derived from primary recipients also rescued Btk-dependent function in secondary hosts that had received a transplant. Together, these data demonstrate that gene transfer into hematopoietic stem cells can reconstitute Btk-dependent B-cell development and function in vivo, and strongly support the feasibility of pursuing Btk gene transfer for XLA.

scholarly journals The Dynamics of B Cell Aging in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Jill de Mol ◽  
Johan Kuiper ◽  
Dimitrios Tsiantoulas ◽  
Amanda C. Foks
Keyword(s):  
B Cells ◽  
B Cell ◽  
Inflammatory Diseases ◽  
Cell Aging ◽  
Chronic Inflammatory Diseases ◽  
Age Related ◽  
T Cell Regulation ◽  
Health And Disease ◽  
B Cell Subsets ◽  
And Function

Aging is considered to be an important risk factor for several inflammatory diseases. B cells play a major role in chronic inflammatory diseases by antibody secretion, antigen presentation and T cell regulation. Different B cell subsets have been implicated in infections and multiple autoimmune diseases. Since aging decreases B cell numbers, affects B cell subsets and impairs antibody responses, the aged B cell is expected to have major impacts on the development and progression of these diseases. In this review, we summarize the role of B cells in health and disease settings, such as atherosclerotic disease. Furthermore, we provide an overview of age-related changes in B cell development and function with respect to their impact in chronic inflammatory diseases.

scholarly journals B-Cell Immunophenotyping to Predict Vaccination Outcome in the Immunocompromised - A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Annieck M. Diks ◽  
Lisanne A. Overduin ◽  
Laurens D. van Leenen ◽  
Lennert Slobbe ◽  
Hetty Jolink ◽  
...  
Keyword(s):  
Immune System ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Plasma Cells ◽  
Vaccination Schedule ◽  
Effective Measure ◽  
Critical Components ◽  
B Cell Subsets ◽  
And Function

Vaccination is the most effective measure to prevent infections in the general population. Its efficiency strongly depends on the function and composition of the immune system. If the immune system lacks critical components, patients will not be fully protected despite a completed vaccination schedule. Antigen-specific serum immunoglobulin levels are broadly used correlates of protection. These are the products of terminally differentiated B cells – plasma cells. Here we reviewed the literature on how aberrancies in B-cell composition and function influence immune responses to vaccinations. In a search through five major literature databases, 6,537 unique articles published from 2000 and onwards were identified. 75 articles were included along three major research lines: extremities of life, immunodeficiency and immunosuppression. Details of the protocol can be found in the International Prospective Register of Systematic Reviews [PROSPERO (registration number CRD42021226683)]. The majority of articles investigated immune responses in adults, in which vaccinations against pneumococci and influenza were strongly represented. Lack of baseline information was the most common reason of exclusion. Irrespective of study group, three parameters measured at baseline seemed to have a predictive value in assessing vaccine efficacy: (1) distribution of B-cell subsets (mostly a reduction in memory B cells), (2) presence of exhausted/activated B cells, or B cells with an aberrant phenotype, and (3) pre-existing immunological memory. In this review we showed how pre-immunization (baseline) knowledge of circulating B cells can be used to predict vaccination efficacy. We hope that this overview will contribute to optimizing vaccination strategies, especially in immunocompromised patients.

CXCR7 Regulates Retention of Splenic Marginal Zone B Cells and Availability of SDF-1/CXCL12

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3902-3902
Author(s):  
Hongsheng Wang ◽  
Dong Mi Shin ◽  
Chenfeng Qi ◽  
Herbert Morse
Keyword(s):  
B Cells ◽  
B Cell ◽  
Marginal Zone ◽  
Conflicts Of Interest ◽  
Gene Profiling ◽  
Marginal Zone B Cells ◽  
B Cell Subsets ◽  
And Function ◽  
Follicular B Cells ◽  
Extracellular Environment

Abstract Abstract 3902 CXCR7 is a newly discovered receptor for the chemokines I-TAC/CXCL11 and SDF-1/CXCL12. Overexpression of CXCR7 in certain tumors has been associated with increased activities of adhesion, invasion and survival. CXCR7 has thus been investigated as a potential chemotherapeutic target in the treatment of metastatic cancers. Our analyses of murine B cell lymphomas revealed that marginal zone B (MZB) cell lymphomas expressed higher levels of CXCR7 than other types of lymphomas. This prompted us to investigate the expression and function of CXCR7 in normal B cells. In this report, we demonstrate that normal MZB cells expressed the highest level of CXCR7 among all B cell subsets. This pattern of expression was consistent with gene profiling studies using cDNA microarrays. Injection of mice with CCX754 or CCX771, a specific blocker of CXCR7, resulted in a significant reduction of MZB cells in the spleen. Immunohistological analyses revealed disrupted integrity and reduced size of the MZ in spleens of CCX754-treated mice. In addition, CCX754 significantly blocked internalization of CXCR7 resulting in an increase of CXCR7 expression on MZB cells but not follicular B cells. This indicates that CXCR7 constantly removes its ligands from the extracellular environment. Taking together, our data suggest that CXCR7 controls CXCL12 availability influencing MZB cell retention in the spleen. Disclosures: No relevant conflicts of interest to declare.

Lymphoproliferative disorders (LPD) involving lungs: T and B cell subsets within pulmonary infiltrates and in peripheral blood

1984 ◽  
Vol 42 ◽  
pp. 700-701
Author(s):  
Irene Stachura ◽  
Milton H. Dalbow ◽  
Michael J. Niemiec ◽  
Matias Pardo ◽  
Gurmukh Singh ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lymphoproliferative Disorders ◽  
Mixed Population ◽  
Lymphoid Cells ◽  
Lymphomatoid Granulomatosis ◽  
Cell Type ◽  
Cell Surface Antigens ◽  
Pulmonary Infiltrates ◽  
B Cell Subsets

Lymphoid cells were analyzed within pulmonary infiltrates of six patients with lymphoproliferative disorders involving lungs by immunofluorescence and immunoperoxidase techniques utilizing monoclonal antibodies to cell surface antigens T11 (total T), T4 (inducer/helper T), T8 (cytotoxic/suppressor T) and B1 (B cells) and the antisera against heavy (G,A,M) and light (kappa, lambda) immunoglobulin chains. Three patients had pseudolymphoma, two patients had lymphoma and one patient had lymphomatoid granulomatosis.A mixed population of cells was present in tissue infiltrates from the three patients with pseudolymphoma, IgM-kappa producing cells constituted the main B cell type in one patient. In two patients with lymphoma pattern the infiltrates were composed exclusively of T4+ cells and IgG-lambda B cells predominated slightly in the patient with lymphomatoid granulomatosis.

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