Advances in Human B Cell Phenotypic Profiling

Kaminski, Denise A.; Wei, Chungwen; Yu, Qian; Rosenberg, Alexander F.; Sanz, Igñacio

doi:10.3389/fimmu.2012.00302

Cited by 242 publications

(289 citation statements)

References 178 publications

(313 reference statements)

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“…The subset of NSM B-cells has been implicated in immune responses against T-cell independent antigens, however recent studies confirmed their role as a long-lasting memory to T-cell dependent antigens involved in reconstitution of switched memory pool upon antigen restimulation [10]. Changes in NSM fraction were accompanied by increased percentage of immature/ /early-transitional B-cells and activated SM cells, both [8,16,23]. Nevertheless, systemic accumulation of B-cells with CD27+CD21 low phenotype, e.g.…”

Section: Discussionmentioning

confidence: 96%

“…Samples were fixed with FACS lysing solution (BD Biosciences), washed and analyzed in FACS Canto II flow cytometer (BD Biosciences). Based on differential expression of surface markers the following B-cell subsets were identified: immature/ /early-transitional (I/T, CD27-IgD+CD21 low ), late-transitional/naïve (CD27-IgD+CD21+), non-switched memory (NSM, CD27+IgD+), resting class-switched memory (SM, CD27+IgD-CD21+), activated SM (CD27+IgD-CD21 low ), and double-negative (CD27-IgD-) exhausted memory (ExM) as summarized in Figure 1C [8,16,23,25]. Using T-cell panel we identified four subsets within CD4+ or CD8+ gate: naïve (CD45RA+CD45RO-CCR7+), central memory (T CM , CD45RA-CD45RO+CCR7+), effector memory (T EM , CD45RA-CD45RO+CCR7-), and effector memory CD45RA+ (T EMRA , CD45RA+CD45RO-CCR7-) [26,27].…”

Section: Methodsmentioning

confidence: 99%

“…Memory B-cells generated during GC reaction can be recognized by surface expression of CD27, and are classified as switched memory cells (SM; CD27+IgD-), or non-switched (i.e. IgM+) memory cells (NSM; CD27+IgD+) [8]. During secondary antigen exposure SM B-cells proliferate rapidly and differentiate into antibody secreting cells, while NSM cells are able to reinitiate GC reaction and replenish SM fraction [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Changes of memory B- and T-cell subsets in lupus nephritis patients

Kosałka

Jakieła

Musiał

2015

Folia Histochem Cytobiol.

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Introduction. Renal involvement in systemic lupus erythematosus (SLE) is associated with production of antibodies to double stranded DNA, deposition of immune complexes and organ damage. These processes have been linked with abnormalities in B-and T-cell memory compartments. The aim of the study was to analyze subsets of peripheral memory B-cells and T-cells in lupus nephritis (LN) patients. Material and methods. We used multicolor flow cytometry to analyze major memory subsets of peripheral blood B-cells (defined by CD27, IgD and CD21) and T-cells (CD45RA, CD45RO, CCR7) in 32 patients with active or inactive LN, and 23 control subjects. Results. Lupus nephritis patients were characterized by increased percentage of immature/early-transitional B-cells (CD27-IgD+CD21-), higher frequency of activated switched memory (SM, CD27+IgD-CD21-) and exhausted memory B-cells (CD27-IgD-), and decrease in non-switched memory (NSM, CD27+IgD+) B-cells. CD21 low subsets (immature and activated B-cells) were particularly expanded in patients with active disease. In both groups of LN patients we observed decline in the absolute count of NSM B-cells. It was paralleled by lymphopenia in naïve CD4+ T-cell compartment and increase in the frequency of effector memory T-cells, and these changes were more pronounced in active LN. Conclusions. B-cell memory compartment in LN is deficient in NSM cells and during active disease it is further skewed towards SM and exhausted memory phenotypes, most likely as a cause of chronic antigenic stimulation. Parallel changes in T-helper cell subsets suggest a similar mechanism of SLE-related lymphopenia for both B-cell and T-cell compartment.

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Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Changes of memory B- and T-cell subsets in lupus nephritis patients

Kosałka

Jakieła

Musiał

2015

Folia Histochem Cytobiol.

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“…Further distinction of B cell subsets within CD27 + and CD27 2 cells may help to further define the relevance of these changes. For example, memory CD27 + B cells can be separated into IgD 2 isotypeswitched and IgD + NSM subsets, and CD27 2 B cells can be separated into IgD + mature naive and IgD 2 SwM-like B cells (107). The importance of distinguishing the latter CD27 2 IgD 2 DN B cells that we and others have shown to be elevated in SLE patients (Fig.…”

Section: Discussionmentioning

confidence: 99%

Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity

Nakayama¹,

Kosek²,

Capone³

et al. 2017

The Journal of Immunology

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BAFF is a B cell survival and maturation factor implicated in the pathogenesis of systemic lupus erythematosus (SLE). In this in vitro study, we describe that soluble BAFF in combination with IL-2 and IL-21 is a T cell contact-independent inducer of human B cell proliferation, plasmablast differentiation, and IgG secretion from circulating CD27+ memory and memory-like CD27−IgD− double-negative (DN) B cells, but not CD27−IgD+ naive B cells. In contrast, soluble CD40L in combination with IL-2 and IL-21 induces these activities in both memory and naive B cells. Blood from healthy donors and SLE patients have similar circulating levels of IL-2, whereas SLE patients exhibit elevated BAFF and DN B cells and reduced IL-21. B cell differentiation transcription factors in memory, DN, and naive B cells in SLE show elevated levels of Aiolos, whereas Ikaros levels are unchanged. Treatment with CC-220, a modulator of the cullin ring ligase 4-cereblon E3 ubiquitin ligase complex, reduces Aiolos and Ikaros protein levels and BAFF- and CD40L-induced proliferation, plasmablast differentiation, and IgG secretion. The observation that the soluble factors BAFF, IL-2, and IL-21 induce memory and DN B cell activation and differentiation has implications for extrafollicular plasmablast development within inflamed tissue. Inhibition of B cell plasmablast differentiation by reduction of Aiolos and Ikaros may have utility in the treatment of SLE, where elevated levels of BAFF and Aiolos may prime CD27+ memory and DN memory-like B cells to become Ab-producing plasmablasts in the presence of BAFF and proinflammatory cytokines.

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“…In particular IgD, CD27, CD24 and CD38, other than other molecules, may be used to study peripheral B cells in humans. Nevertheless "core" subsets may be identified by using IgD and CD27 expression on CD19 B cells and this kind of classification has been suggested to be useful as potential biomarkers in some autoimmune diseases (Kaminski et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Trafficking phenotype and production of granzyme B by double negative B cells (IgG+IgD−CD27−) in the elderly

Bulati

Buffa

Martorana

et al. 2014

Experimental Gerontology

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The impairment of humoral immune response in elderly humans has been extensively demonstrated. We have reported the increase of memory B cells (IgG, double negative, DN) population in the elderly, in which there is also a typical inflammatory micro-environment. In order to evaluate whether this pro-inflammatory status could influence the trafficking phenotype of naïve/memory B cells, we have assessed the expression of CCR7, CCR6, CXCR3, CXCR4, CXCR5 and CD62L on naïve/memory B cell subpopulations in young and elderly subjects. Moreover, the combination of pro-inflammatory interleukin-21 (IL-21) and B cell receptor (BCR) stimulation enables B cells to produce and secrete granzyme B (GrB), which plays a critical role in early anti-viral immune responses, in the regulation of autoimmune mechanisms and in cancer immunosurveillance. Our data demonstrate that in the elderly, naïve/memory B cell populations present a different expression of the studied receptors that could be discussed in terms of "inflamm-aging". In particular IgGshow a tissue trafficking phenotype and they can be stimulated to produce GrB.

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Advances in Human B Cell Phenotypic Profiling

Cited by 242 publications

References 178 publications

Changes of memory B- and T-cell subsets in lupus nephritis patients

Changes of memory B- and T-cell subsets in lupus nephritis patients

Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity

Trafficking phenotype and production of granzyme B by double negative B cells (IgG+IgD−CD27−) in the elderly

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