330 Characterization of multiple B cell subsets in peripheral blood of psoriasis patients identifies a correlation of regulatory B cells and disease severity

ABSTRACTMeasles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils toin vitroMV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (TH) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that TH1TH17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression.IMPORTANCEMeasles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the importance of MV infection of B cellsin vivo. However, information on the relative susceptibility of B-cell subsets is scarce. Here, we compared the susceptibility and permissiveness toin vitroMV infection of human naive and memory T- and B-cell subsets isolated from peripheral blood or tonsils. Our results demonstrate that both naive and memory B cells are more permissive to MV infection than T cells. The highest infection levels were detected in plasma cells and germinal center B cells, suggesting that infection and depletion of these populations contribute to reduced host resistance.

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IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4–, MyD88-, and TIRAP- but not UNC-93B–deficient patients

Blood ◽

10.1182/blood-2012-07-440776 ◽

2012 ◽

Vol 120 (25) ◽

pp. 4992-5001 ◽

Cited By ~ 63

Author(s):

Sandra Weller ◽

Mélanie Bonnet ◽

Héloïse Delagreverie ◽

Laura Israel ◽

Maya Chrabieh ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Signaling Pathways ◽

Size Distribution ◽

Heavy Chain ◽

Peripheral Blood ◽

Somatic Hypermutation ◽

Key Factors ◽

Tlr Signaling ◽

B Cell Subsets

Abstract We studied the distribution of peripheral B-cell subsets in patients deficient for key factors of the TLR-signaling pathways (MyD88, TIRAP/MAL, IL-1 receptor–associated kinase 4 [IRAK-4], TLR3, UNC-93B, TRIF). All TLRs, except TLR3, which signals through the TRIF adaptor, require MyD88 and IRAK-4 to mediate their function. TLR4 and the TLR2 heterodimers (with TLR1, TLR6, and possibly TLR10) require in addition the adaptor TIRAP, whereas UNC-93B is needed for the proper localization of intracellular TLR3, TLR7, TLR8, and TLR9. We found that IgM+IgD+CD27+ but not switched B cells were strongly reduced in MyD88-, IRAK-4-, and TIRAP-deficient patients. This defect did not appear to be compensated with age. However, somatic hypermutation of Ig genes and heavy-chain CDR3 size distribution of IgM+IgD+CD27+ B cells were not affected in these patients. In contrast, the numbers of IgM+IgD+CD27+ B cells were normal in the absence of TLR3, TRIF, and UNC-93B, suggesting that UNC-93B–dependent TLRs, and notably TLR9, are dispensable for the presence of this subset in peripheral blood. Interestingly, TLR10 was found to be expressed at greater levels in IgM+IgD+CD27+ compared with switched B cells in healthy patients. Hence, we propose a role for TIRAP-dependent TLRs, possibly TLR10 in particular, in the development and/or maintenance of IgM+IgD+CD27+ B cells in humans.

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Phenotypic and Molecular Characterization of Human Peripheral Blood B-cell Subsets with Special Reference to N-Region Addition and Jκ-Usage in VκJκ-Joints and κ/λ-Ratios ixn Naive Versus Memory B-cell Subsets to Identify Traces of Receptor Editing Processes

Current Topics in Microbiology and Immunology - Mechanisms of B Cell Neoplasia 1998 ◽

10.1007/978-3-642-60162-0_18 ◽

1999 ◽

pp. 141-147 ◽

Cited By ~ 5

Author(s):

U. Klein ◽

K. Rajewsky ◽

R. Küppers

Keyword(s):

B Cell ◽

Special Reference ◽

Molecular Characterization ◽

Peripheral Blood ◽

Human Peripheral Blood ◽

Receptor Editing ◽

Memory B Cell ◽

B Cell Subsets

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OP0024 DECREASED LEVELS OF T FOLLICULAR HELPER (CD4+CXCR5+) CELLS AND CD27+CD38+ AND CD27+CD38- B CELLS IN ANKYLOSING SPONDYLITIS PATIENTS CORRELATE WITH MARKER OF INFLAMMATION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.785 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 13.2-14

Author(s):

H. Forsblad-D’elia ◽

U. Hellman ◽

A. Kumar ◽

K. Lejon

Keyword(s):

Ankylosing Spondylitis ◽

B Cells ◽

B Cell ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Female Patients ◽

Tfh Cells ◽

Follicular Helper ◽

B Cell Subsets

Background:The role of different lymphocyte subsets in ankylosing spondylitis (AS) is still to be elucidated. It has previously been reported contradictory data concerning the levels of T Follicular Helper (TFH) cells and differentiated B cells in peripheral blood of AS patients. In addition, the connection to disease related parameters is still to be fully revealed.Objectives:The purpose of this study was to investigate the level of CD4+TFH cells and CD27+CD38+/CD38- B cells in patients with AS from northern Sweden and to compare the levels with age and sex-matched controls. We also studied associations between these cell subsets and disease related factors.Methods:Peripheral blood mononuclear cells (PBMSc) from a cohort of 50 patients with AS from Region Västerbotten (mean age 52±9.1 years, 33 (66 %) men, 50 (100 %) HLAB27 positive) and 50 pair wise matched blood donor controls (mean age 54±8.8 years, 33 (66 %) men) were stained with a combination of antibodies allowing for the detection of CD27, CD38, CD19, CD3, CD4 and CXCR5 markers and analyzed by flow cytometry. In addition, the patient with AS were examined with spinal x-ray for radiographic alterations assessed with mSASSS. CRP and ESR were measured and physical function and disease activity were registered with BASMI and BASFI respectively ASDAS-CRP and BASDAI.Results:When comparing AS patients and controls pair wise, we observed on average a 50% reduction of TFH (CD3+CD4+CXCR5+) cells among CD45+ lymphocytes in PBMCs from patients (p=0,000008). Furthermore, a 20-30% reduction among memory/plasma cells (CD19+CD27+CD38+ and CD19+CD27+CD38-) among CD45+ lymphocytes in PBMCs from patients (p=0,002 and p=0,007 respectively). For female patients a correlation between TFH and ESR (Rs=-0,551 p=0,022) was observed. Moreover, negative correlations between the two B cell subsets (CD19+CD27+CD38+ and CD19+CD27+CD38-) and ESR were observed for female patients (Rs =–0,476 p=0,053 and Rs =–0,522 p=0,032 respectively).Conclusion:TFH cells was reduced in AS patients and this reduction correlated with a reduction in differentiated (CD27+CD38+ and CD27+CD38-) B cells. In addition, the inflammation marker ESR was negatively correlated with TFH as well as with the differentiated B cell subsets in female patients. Our observations indicates a role of the humoral immune response in AS.Disclosure of Interests:None declared

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Presence of intragraft B cells during acute renal allograft rejection is accompanied by changes in peripheral blood B cell subsets

Clinical & Experimental Immunology ◽

10.1111/cei.13269 ◽

2019 ◽

Vol 196 (3) ◽

pp. 403-414 ◽

Cited By ~ 1

Author(s):

S. Heidt ◽

M. Vergunst ◽

J. D. H. Anholts ◽

G. M. J. S. Swings ◽

E. M. J. Gielis ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Peripheral Blood ◽

Allograft Rejection ◽

Renal Allograft ◽

Renal Allograft Rejection ◽

Acute Renal Allograft Rejection ◽

B Cell Subsets

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CD19+ B cell subsets in the peripheral blood and skin lesions of psoriasis patients and their correlations with disease severity

Brazilian Journal of Medical and Biological Research ◽

10.1590/1414-431x20165374 ◽

2016 ◽

Vol 49 (9) ◽

Cited By ~ 11

Author(s):

J. Lu ◽

Y. Ding ◽

X. Yi ◽

J. Zheng

Keyword(s):

B Cell ◽

Disease Severity ◽

Peripheral Blood ◽

Skin Lesions ◽

B Cell Subsets

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Characteristics of CD11c+CD5+ chronic B-cell leukemias and the identification of novel peripheral blood B-cell subsets with chronic lymphoid leukemia immunophenotypes [see comments]

Blood ◽

10.1182/blood.v76.1.123.bloodjournal761123 ◽

1990 ◽

Vol 76 (1) ◽

pp. 123-130 ◽

Cited By ~ 1

Author(s):

SB Wormsley ◽

SM Baird ◽

N Gadol ◽

KR Rai ◽

RE Sobol

Keyword(s):

B Cells ◽

B Cell ◽

Peripheral Blood ◽

Small Lymphocyte ◽

Lymphoid Leukemia ◽

Color Flow ◽

Prolymphocytic Leukemia ◽

Normal Peripheral Blood ◽

Chronic Lymphoid Leukemia ◽

B Cell Subsets

Previous studies have indicated that chronic lymphocytic leukemias (CLL) are characterized by the coexpression of CD5 and B-cell antigens, while hairy cell leukemias (HCL) typically express CD11c+CD5- B-cell immunophenotypes. In this report we describe the features of B-cell leukemias with CD11c+CD5+ immunophenotypes and the identification of novel circulating B-cell subsets defined by the expression of CD20, CD5, and CD11c antigens. Morphologic evaluation of 14CD11c+CD5+ B-cell leukemias showed that they generally had larger cellular diameters (14 to 21 microns) and lower nuclear:cytoplasm ratios than typical small lymphocyte CLL. These cases did not exhibit the well-defined nucleoli characteristic of prolymphocytic leukemia (PLL). The presenting clinical features of CD11c+CD5+ B-cell leukemias were most consistent with CLL or PLL, and none of the evaluated cases had pancytopenia, splenomegaly, and cytoplasmic villi characteristic of HCL. Examination of normal peripheral blood (n = 6) by three-color flow cytometry identified four novel B-cell subsets with the following immunophenotypes (mean percent of total CD20+ B cells +/- SE): CD20+CD5+CD11c+ (8.0 +/- 1.6); CD20+CD5-CD11c+ (12.0 +/- 2.0); CD20+CD5+CD11c- (35.0 +/- 4.9); and CD20+CD5-CD11c- (44.0 +/- 5.0). Our findings suggest that CD11c+CD5+ B-cell leukemias with atypical morphologic features represent forms of CLL or PLL rather than HCL. In addition, we have identified novel subsets of circulating B cells defined by patterns of CD20, CD5, and CD11c expression that correspond to the immunophenotypes of chronic B-cell leukemias.

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Characterization of Definitive Regulatory B Cell Subsets by Cell Surface Phenotype, Function and Context

Frontiers in Immunology ◽

10.3389/fimmu.2021.787464 ◽

2021 ◽

Vol 12 ◽

Author(s):

Savannah D. Neu ◽

Bonnie N. Dittel

Keyword(s):

B Cells ◽

B Cell ◽

Clinical Settings ◽

Autoimmune Encephalomyelitis ◽

Regulatory B Cell ◽

Broad Term ◽

B Cell Subsets ◽

Experimental Autoimmune ◽

Identification Strategy

Regulatory B cell or “Breg” is a broad term that represents the anti-inflammatory activity of B cells, but does not describe their individual phenotypes, specific mechanisms of regulation or relevant disease contexts. Thus, given the variety of B cell regulatory mechanisms reported in human disease and their animal models, a more thorough and comprehensive identification strategy is needed for tracking and comparing B cell subsets between research groups and in clinical settings. This review summarizes the discovery process and mechanism of action for well-defined regulatory B cell subsets with an emphasis on the mouse model of multiple sclerosis experimental autoimmune encephalomyelitis. We discuss the importance of conducting thorough B cell phenotyping along with mechanistic studies prior to defining a particular subset of B cells as Breg. Since virtually all B cell subsets can exert regulatory activity, it is timely for their definitive identification across studies.

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Pharmacodynamic Effects of Administration of Maytansine Conjugated Anti-CD22 Monoclonal Antibodies to Cynomolgus Monkeys

Blood ◽

10.1182/blood.v112.11.4996.4996 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4996-4996

Author(s):

Franklin Fuh ◽

Reina Fuji ◽

Kirsten A Poon ◽

Dongwei Li ◽

Clarissa David ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

B Cell ◽

Peripheral Blood ◽

Lymphoid Tissues ◽

Marginal Zone B Cells ◽

Cynomolgus Monkeys ◽

Pharmacodynamic Effects ◽

Pharmacodynamic Profile ◽

B Cell Subsets

Abstract CD22 is a B cell-specific glycoprotein expressed on the cell surface of all mature B cells. A candidate therapeutic anti-CD22 antibody, 10F4v3, was conjugated to the anti-mitotic agent maytansine (10F4v3-DM1). DM1 disrupts cellular mitosis through inhibition of tubulin polymerization when internalized into cells. The anti-CD22 DM1 conjugate was shown to have significant potency in preclinical efficacy models of NHL. In order to further characterize this antibody-drug conjugate in preclinical studies, we first evaluated the binding characteristics of the 10F4v3 to peripheral blood B cells from various geographical sources of cynomolgus monkeys. 10F4v3 bound to peripheral blood B cells from all cynomolgus monkeys of Indonesian and Mauritian origins, but displayed only limited binding to cynomolgus monkeys of Chinese and Cambodian origins. Therefore, further pre-clinical evaluation of 10F4v3-DM1 was conducted in Indonesian cynomolgus monkeys to examine the safety, pharmacokinetic, and pharmacodynamic effects in monkeys dosed at 10, 20, and 30 mg/kg (2000, 4000, and 6000 mg/m2 DM1). Pharmacodynamic assessments of peripheral blood and lymphoid tissues included examination of B cells, B cell subsets, CD4+ T cells, CD8+ T cells, and CD3−CD20− (NK) cells. B cell subsets included CD20+, CD20+CD21+, CD20+CD21−, CD20+CD21+CD27+, CD20+CD21+CD27−, and CD20+CD21high lymphocytes which are phenotypically similar to human B cells, mature B cells, germinal center B cells, memory B cells, naïve B cells, and marginal zone B cells, respectively. B cells and B cell subsets were substantially depleted in peripheral blood at all doses, with no apparent dose-dependent effects. In lymphoid tissue, B cells were also depleted, with substantial depletion of CD20+CD21− and CD20+CD21high B cell subsets in spleen and bone marrow. Based on the nonclinical data, 10F4v3-DM1 exhibits an encouraging pharmacodynamic profile that supports clinical development for the potential treatment of non-Hodgkin’s lymphoma.

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Circulating CD19+CD24hiCD38hi regulatory B cells as biomarkers of response to methotrexate in early rheumatoid arthritis

Rheumatology ◽

10.1093/rheumatology/keaa186 ◽

2020 ◽

Vol 59 (10) ◽

pp. 3081-3091

Author(s):

Paula Fortea-Gordo ◽

Alejandro Villalba ◽

Laura Nuño ◽

María José Santos-Bórnez ◽

Diana Peiteado ◽

...

Keyword(s):

T Cell ◽

B Cells ◽

B Cell ◽

Clinical Response ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Regulatory B Cells ◽

Cell Frequency ◽

Peripheral Blood Mononuclear ◽

Inflammatory Conditions

Abstract Objective The protagonism of regulatory B cells seems to vary along the course of the disease in murine models of inflammatory conditions. Decreased numbers of circulating regulatory CD19+CD24hiCD38hi transitional (cTr) B cells have been described in patients with long-standing RA, thus our objective was to examine the frequency and evolution of cTr B cells in the peripheral blood of early RA (ERA) patients. Methods Freshly isolated peripheral blood mononuclear cells from 48 steroid- and DMARD-naïve ERA patients with a disease duration of <24 weeks and 48 healthy controls (HCs) were examined by flow cytometry. Co-cultures of isolated memory B cells were established with autologous T cells in the absence or presence of Tr B cells. Results As compared with HCs, ERA patients demonstrated an increased frequency of cTr B cells. cTr B cells of ERA patients and HCs displayed an anti-inflammatory cytokine profile and were able to downregulate T cell IFN-γ and IL-21 production, together with ACPA secretion in autologous B/T cell co-cultures. Basal frequencies of cTr B cells above the median value observed in HCs were associated with a good EULAR response to MTX at 12 months [relative risk 2.91 (95% CI 1.37, 6.47)]. A significant reduction of cTr B cells was observed 12 months after initiating MTX, when the cTr B cell frequency was no longer elevated but decreased, and this was independent of the degree of clinical response or the intake of prednisone. Conclusion An increased frequency of regulatory cTr B cells is apparent in untreated ERA and the baseline cTr B cell frequency is associated with the clinical response to MTX at 12 months.

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