scholarly journals B Cells in Teleost Fish Act as Pivotal Initiating APCs in Priming Adaptive Immunity: An Evolutionary Perspective on the Origin of the B-1 Cell Subset and B7 Molecules

2014 ◽  
Vol 192 (6) ◽  
pp. 2699-2714 ◽  
Author(s):  
Lv-yun Zhu ◽  
Ai-fu Lin ◽  
Tong Shao ◽  
Li Nie ◽  
Wei-ren Dong ◽  
...  
Keyword(s):  
B Cells ◽  
Adaptive Immunity ◽  
Teleost Fish ◽  
Cell Subset ◽  
Evolutionary Perspective ◽  
B7 Molecules

scholarly journals Hyper‐metabolic B cells in the spleens of old mice make antibodies with autoimmune specificities

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniela Frasca ◽  
Maria Romero ◽  
Denisse Garcia ◽  
Alain Diaz ◽  
Bonnie B. Blomberg
Keyword(s):  
B Cells ◽  
B Cell ◽  
Inflammatory Markers ◽  
Cell Subset ◽  
Antibody Responses ◽  
Metabolic Phenotype ◽  
Cellular Mechanisms ◽  
Autoimmune Antibodies ◽  
B Cell Subsets ◽  
Old Mice

Abstract Background Aging is associated with increased intrinsic B cell inflammation, decreased protective antibody responses and increased autoimmune antibody responses. The effects of aging on the metabolic phenotype of B cells and on the metabolic programs that lead to the secretion of protective versus autoimmune antibodies are not known. Methods Splenic B cells and the major splenic B cell subsets, Follicular (FO) and Age-associated B cells (ABCs), were isolated from the spleens of young and old mice and left unstimulated. The RNA was collected to measure the expression of markers associated with intrinsic inflammation and autoimmune antibody production by qPCR. B cells and B cell subsets were also stimulated with CpG and supernatants collected after 7 days to measure autoimmune IgG secretion by ELISA. Metabolic measures (oxygen consumption rate, extracellular acidification rate and glucose uptake) were performed using a Seahorse XFp extracellular flux analyzer. Results Results have identified the subset of ABCs, whose frequencies and numbers increase with age and represent the most pro-inflammatory B cell subset, as the cell type mainly if not exclusively responsible for the expression of inflammatory markers and for the secretion of autoimmune antibodies in the spleen of old mice. Hyper-inflammatory ABCs from old mice are also hyper-metabolic, as compared to those from young mice and to the subset of FO B cells, a feature needed not only to support their higher expression of RNA for inflammatory markers but also their higher autoimmune antibody secretion. Conclusions These results identify a relationship between intrinsic inflammation, metabolism and autoimmune B cells and suggest possible ways to understand cellular mechanisms that lead to the generation of pathogenic B cells, that are hyper-inflammatory and hyper-metabolic, and secrete IgG antibodies with autoimmune specificities.

scholarly journals OP0186 CHANGES IN CIRCULATING B CELL LEVELS AND IMMUNOPHENOTYPE ARE ASSOCIATED WITH DEVELOPMENT OF ARTHRITIS FOLLOWING TREATMENT WITH CHECKPOINT INHIBITORS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 112.2-113
Author(s):  
M. Gatto ◽  
S. Bjursten ◽  
C. Jonell ◽  
C. Jonsson ◽  
S. Mcgrath ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
B Cells ◽  
Adverse Events ◽  
B Cell ◽  
Mononuclear Cells ◽  
Checkpoint Inhibitors ◽  
Therapy Monitoring ◽  
Cell Subset ◽  
Peripheral Blood Mononuclear ◽  
Transitional B Cells

Background:Inflammatory arthritis (IA) is frequent among rheumatic side effects induced by checkpoint inhibitor (CPI) therapy for metastatic malignancies1. While T cells are likely to sustain the inflammatory process2, fewer data are available concerning the role of B cells3.Objectives:To investigate the phenotype of circulating B cells in patients who develop CPI-induced IA (CPI-IA) and to compare it with features of B cells in patients not developing immune-related adverse events (irAE) upon CPI treatment.Methods:B cell subsets at baseline (before CPI initiation) and during CPI treatment were analyzed in CPI-IA patients and in patients receiving CPI but who did not develop irAE (non-irAE). Peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry and B cells were identified as CD19+ and divided into naïve (CD27-IgD+), memory (CD27+IgD+/-), double negative (CD27-IgD-) and transitional (CD10+CD24+CD38+/hi) B cells. Levels of CD21, an activation marker on transitional B cells, were also analyzed. Non-parametric tests were used for analysis of differences between groups.Results:Six CPI-IA and 7 non-irAE patients matched for age, gender and CPI treatment were included, who had received CPI treatment due to metastatic melanoma. Flow cytometry revealed a significant increase of circulating B cells (p=0.002) (Figure 1A) and especially of transitional B cells in CPI-IA patients vs. non-irAE (median %, range: 7.8 (4.5-11.4) vs. 3.2 (1.6-4.3),p=0.007) (Figure 1B), while no remarkable changes were seen across other subsets. Transitional B cell levels significantly decreased from active to quiescent CPI-IA in all patients (p=0.008). In two CPI-IA patients for whom baseline sampling was available, the increase of transitional levels occurred early after CPI treatment and before CPI-IA onset. Levels of expression of CD21 on transitional B cells were increased in CPI-IA vs. non-irAE (p=0.01).Conclusion:Transitional B cells are expanded in CPI-IA patients and seem to increase early after start of CPI therapy. Monitoring this B cell subset might lead to closer follow-up and earlier diagnosis of CPI-IA.References:[1]Ramos-Casals M, Brahmer JR, Callahan MK, et al. Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primers 2020;6:38[2]Murray-Brown W, Wilsdon TD, Weedon H, et al. Nivolumab-induced synovitis is characterized by florid T cell infiltration and rapid resolution with synovial biopsy-guided therapy. J Immunother Cancer 2020;8:e000281[3]Das R, Bar N, Ferreira M, et al. Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J Clin Invest. 2018;128:715-2Disclosure of Interests:None declared

scholarly journals Genomic Uracil and Aberrant Profile of Demethylation Intermediates in Epigenetics and Hematologic Malignancies

2021 ◽  
Vol 22 (8) ◽  
pp. 4212
Author(s):  
Ryszard Olinski ◽  
Geir Slupphaug ◽  
Marek Foksinski ◽  
Hans Einar Krokan
Keyword(s):  
B Cells ◽  
Adaptive Immunity ◽  
Somatic Hypermutation ◽  
Hematologic Malignancies ◽  
Living Cells ◽  
Oxidation Products ◽  
Epigenetic Mark ◽  
Active Demethylation ◽  
Dna Base ◽  
Natural Modification

DNA of all living cells undergoes continuous structural and chemical alterations resulting from fundamental cellular metabolic processes and reactivity of normal cellular metabolites and constituents. Examples include enzymatically oxidized bases, aberrantly methylated bases, and deaminated bases, the latter largely uracil from deaminated cytosine. In addition, the non-canonical DNA base uracil may result from misincorporated dUMP. Furthermore, uracil generated by deamination of cytosine in DNA is not always damage as it is also an intermediate in normal somatic hypermutation (SHM) and class shift recombination (CSR) at the Ig locus of B-cells in adaptive immunity. Many of the modifications alter base-pairing properties and may thus cause replicative and transcriptional mutagenesis. The best known and most studied epigenetic mark in DNA is 5-methylcytosine (5mC), generated by a methyltransferase that uses SAM as methyl donor, usually in CpG contexts. Oxidation products of 5mC are now thought to be intermediates in active demethylation as well as epigenetic marks in their own rights. The aim of this review is to describe the endogenous processes that surround the generation and removal of the most common types of DNA nucleobase modifications, namely, uracil and certain epigenetic modifications, together with their role in the development of hematological malignances. We also discuss what dictates whether the presence of an altered nucleobase is defined as damage or a natural modification.

scholarly journals AB0060 INCREASED AGE/AUTOIMMUNE-ASSOCIATED B CELLS IN RA AND CLINICAL IMPLICATIONS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1061.3-1061
Author(s):  
Y. Qin ◽  
Z. Chen
Keyword(s):  
B Cells ◽  
Disease Activity ◽  
Inflammatory Cell ◽  
Cell Subset ◽  
Disease Status ◽  
Low Disease Activity ◽  
Rheumatoid Arthritis Joint ◽  
Healthy Control ◽  
Synovial Tissues

Background:Age/Autoimmune-associated B cells (ABCs) are an emerging B cell subset that accumulate in aged and autoimmune-prone mice. Expansion of human ABCs has been observed in patients with autoimmune diseases like SLE and correlated with disease activity. However, it is less known whether ABCs contribute to the pathogenesis of RA.Objectives:The aim of this work was to explore the role of ABCs in RA.Methods:83 RA patients who met the 2010 ACR classification criteria for RA, 42 sex and age matched healthy control (HC), 35 Spondyloarthritis (SpA) and 31 Osteoarthritis (OA) patients were enrolled and blood samples were collected. The proportion of circulating ABCs was detected by flow cytometry and association with clinical and laboratory parameters were analyzed. Expression of characteristic proteins and inflammatory cytokines on ABCs were examined by quantitative real-time PCR.Results:The proportion of ABCs, defined as CD19+CD27-IgD-CD21-CD11c+, was significantly elevated in RA patients, compared with HC, SpA and OA patients. The frequency of ABCs was higher in patients with high disease activity (DAS28>3.2) compared with remission and low disease activity (DAS28<3.2). There was a positive correlation of ABCs with SJC, TJC, DAS28 whereas no association with RF and anti-CCP titer were observed. In addition, increased mRNA expression levels of T-bet, IL-21, MAF and IL-17 were noted on ABCs compared with CD19+CD27-CD11c- B cells.Conclusion:ABCs were expanded in RA patients and associated with active disease status. It might contribute to RA development by production of IL-17.References:[1]Cancro, M.P., Age-Associated B Cells. Annu Rev Immunol, 2020. 38(315-340).[2]F. Zhang, K. Wei, K. Slowikowski et al., Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol 2019, 20, 928-942.Disclosure of Interests:None declared

scholarly journals Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis

Nature ◽  
2017 ◽  
Vol 542 (7639) ◽  
pp. 110-114 ◽  
Author(s):  
Deepak A. Rao ◽  
Michael F. Gurish ◽  
Jennifer L. Marshall ◽  
Kamil Slowikowski ◽  
Chamith Y. Fonseka ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Cell Subset ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Helper Cell Subset

scholarly journals Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. II. Terminal differentiation of postswitch sIgA-bearing Peyer's patch B cells.

1983 ◽  
Vol 158 (3) ◽  
pp. 649-669 ◽  
Author(s):  
H Kawanishi ◽  
L Saltzman ◽  
W Strober
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Present Report ◽  
Protein A ◽  
Cell Subset ◽  
Terminal Differentiation ◽  
Lymphoid Tissues ◽  
T Cell Subset ◽  
Iga Production

Our previous studies indicated that cloned T cells obtained from Peyer's patches (PP) (Lyt-1+, 2-, Ia+, and H-2K/D+) evoked immunoglobulin (Ig) class switching of PP B cells from sIgM to sIgA cells in vitro; however, these switch T cells could not in themselves provide optimal help for the differentiation of postswitch sIgA-bearing PP B cells to IgA-secreting cells. Thus, in the present report we described studies focused on mechanisms regulating terminal differentiation of the postswitch PP sIgA-bearing B cells. First, to explore the effect of T cell-derived B cell differentiation factor(s) (BCDF) and macrophage factor(s) (MF) on the terminal maturation of PP B cells, LPS-stimulated PP B cells were co-cultured for 7 d with cloned T cells in the presence or absence of the above factors. In the absence of PP cloned T cells the BCDF and MF had only a modest effect on IgA production, whereas in the presence of PP, but not spleen cloned T cells, IgA production was increased. Next, to investigate the effect of T cells derived from a gut-associated lymphoid tissue (GALT), mesenteric lymph nodes (MLN), as well as from spleen on terminal differentiation of postswitch sIgA PP B cells, LPS-driven PP B cells were precultured with the cloned T cells to induce a switch to sIgA, and subsequently cultured with MLN or spleen T cells or a Lyt-2+-depleted T cell subset in the presence of a T-dependent polyclonal mitogen, staphylococcal protein A. Alternatively, in the second culture period BCDF alone was added, instead of T cells and protein A. Here it was found that B cells pre-exposed to switch T cells from PP, but not spleen, were induced to produce greatly increased amounts of IgA in the presence of protein A and T cells or a Lyt-2+-depleted T cell subset as well as in the presence of BCDF alone. Furthermore, in the presence of BCDF alone many B cells expressed cytoplasmic IgA. These observations strongly support the view that the terminal differentiation of postswitch sIgA B cells is governed by helper T cells and macrophages, or factors derived from such cells. Such cells or factors do not affect preswitch B cells.

CD5+/Mac-1− peritoneal B cells: A novel B cell subset that exhibits characteristics of B-1 cells

2006 ◽  
Vol 105 (1) ◽  
pp. 90-96 ◽  
Author(s):  
W HASTINGS ◽  
S GURDAK ◽  
J TUMANG ◽  
T ROTHSTEIN
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Subset

scholarly journals CD1c but neither CD1a nor CD1b molecules are expressed on normal, activated, and malignant human B cells: identification of a new B-cell subset

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 241-247 ◽  
Author(s):  
D Delia ◽  
G Cattoretti ◽  
N Polli ◽  
E Fontanella ◽  
A Aiello ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
De Novo ◽  
Cell Subset ◽  
Ultrastructural Level ◽  
Cytoplasmic Staining ◽  
Clear Cut ◽  
Hodgkin's Lymphomas

Abstract The CD1 cluster of monoclonal antibodies (MoAbs) CD1a, CD1b, and CD1c, identifies molecules that are differentially expressed on hematopoietic and nonhematopoietic tissues. Our earlier finding that the mantle zone (MZ) but not the germinal center (GC) of normal lymph nodes (LN) is CD1c+, CD1a-, and CD1b- prompted us to further investigate the expression of these molecules on normal, activated, and malignant B cells. We report that blood and spleen contain CD1c+ B cells that account for 49% +/- 20.4% (mean +/- SD) and 50.9% +/- 4.4% of the total B cell population, respectively. CD1a- and CD1b-specific MoAbs are unreactive with both B and T cells; these latter are CD1c- as well. When CD1c+ and CD1c- B cells are activated in vitro, the CD1c molecule is upregulated in the former subset and induced de novo in the latter. Conversely, activated blood T cells remain CD1c-. Neither CD1a nor CD1b molecules are detected on activated T and B lymphocytes. At ultrastructural level, the CD1c+ B cells exhibit distinctive features, namely, condensed chromatin with or without a nucleolus and a unique cluster of cytoplasmic vesicles and organelles; the number of nucleolated cells is higher in the spleen (95%) than in the tonsil (40%) or blood (5%). These findings further confirm the similarity between blood and MZ B cells. The CD1c expression assessed on 27 B-cell chronic lymphocytic leukemias (B-CLL) and 46 B non-Hodgkin's lymphomas (B-NHL) was detected on 41% and 32% of cases, respectively; the latter comprised four follicular and 11 diffuse histotypes. The Burkitt's lymphomas were CD1c-negative. The B-cell neoplasms were all CD1a- and, except for four with a weak cytoplasmic staining, all CD1b- as well. The clear-cut CD1c distribution in normal LN (MZ+, GC-) contrasted with the evidence that some B-NHL cells of GC origin (eg, follicular with predominantly small cleaved cells) were CD1c+. Overall, the finding that CD1c expression is restricted to a fraction of B cells present in lymphoid organs and in peripheral blood indicates that CD1c is a powerful marker for the identification and dissection of B-cell subsets whose functional properties can now be evaluated.

scholarly journals Proportions of B-cell subsets are altered in incomplete systemic lupus erythematosus and correlate with interferon score and IgG levels

Rheumatology ◽  
2020 ◽  
Vol 59 (9) ◽  
pp. 2616-2624
Author(s):  
Svenja Henning ◽  
Wietske M Lambers ◽  
Berber Doornbos-van der Meer ◽  
Wayel H Abdulahad ◽  
Frans G M Kroese ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Subset ◽  
Cross Sectional Study ◽  
Type I ◽  
Healthy Controls ◽  
Sectional Study ◽  
Cross Sectional ◽  
B Cell Subsets

Abstract Objectives Incomplete SLE (iSLE) patients display symptoms typical for SLE but have insufficient criteria to fulfil the diagnosis. Biomarkers are needed to identify iSLE patients that will progress to SLE. IFN type I activation, B-cell-activating factor (BAFF) and B-cell subset distortions play an important role in the pathogenesis of SLE. The aim of this cross-sectional study was to investigate whether B-cell subsets are altered in iSLE patients, and whether these alterations correlate with IFN scores and BAFF levels. Methods iSLE patients (n = 34), SLE patients (n = 41) with quiescent disease (SLEDAI ≤4) and healthy controls (n = 22) were included. Proportions of B-cell subsets were measured with flow cytometry, IFN scores with RT-PCR and BAFF levels with ELISA. Results Proportions of age-associated B-cells were elevated in iSLE patients compared with healthy controls and correlated with IgG levels. In iSLE patients, IFN scores and BAFF levels were significantly increased compared with healthy controls. Also, IFN scores correlated with proportions of switched memory B-cells, plasma cells and IgG levels, and correlated negatively with complement levels in iSLE patients. Conclusion In this cross-sectional study, distortions in B-cell subsets were observed in iSLE patients and were correlated with IFN scores and IgG levels. Since these factors play an important role in the pathogenesis of SLE, iSLE patients with these distortions, high IFN scores, and high levels of IgG and BAFF may be at risk for progression to SLE.

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