Peripheral B cell abnormalities in patients with systemic lupus erythematosus in quiescent phase: Decreased memory B cells and membrane CD19 expression

Korganow, Anne‐Sophie; Knapp, Anne‐Marie; Nehme-Schuster, H.; Soulas-Sprauel, Pauline; Poindron, Vincent; Pasquali, Jean‐Louis; Martin, Thierry

doi:10.1016/j.jaut.2009.11.002

Cited by 54 publications

(46 citation statements)

References 51 publications

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“…However, there were no morphological differences between cells categorized as CD20 weak or normal by FCM. In B-cell lymphoma, a silenced PAX-5 determines commitment to plasma cell differentiation [26]. Nevertheless, all cases in this study were CD19 positive by FCM.…”

Section: Morphologymentioning

confidence: 58%

Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL

et al. 2012

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Diffuse large B-cell lymphomas (DLBCL) express CD20. CD20 expression is described as negative, weak, or normal as determined by flow cytometry (FCM) and is an important target for the treatment of DLBCL. However, the impact of CD20 levels at onset of the disease on patient prognosis has not been fully elucidated. We analyzed 174 DLBCL cases newly diagnosed between January 1998 and April 2010. The relationship of the association between CD20 levels and patients' backgrounds and prognoses was analyzed using the Kaplan-Meier method and Cox proportional hazard regression. Of the 174 patients, three cases (1.7%) were defined as CD20 negative based on immunohistochemistry (IHC). Although the other 171 cases were positive by IHC, eight cases (4.7%) were defined as negative and 33 cases (19.3%) were defined as weak when analyzed by FCM. Of the 105 patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy, those who were CD20 negative (FCM) showed significantly inferior overall (hazard ratios (HR): 6.79, 95% CI: 1.32-34.96, p = 0.04) and progression-free survival (HR: 7.3, 95% CI: 1.49-35.8, p = 0.04) compared to patients who were CD20 normal. Our findings indicate that the CD20 level (FCM) at onset is an independent predictor of the prognosis of patients with DLBCL.

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Section: Morphologymentioning

confidence: 58%

Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL

et al. 2012

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“…The reduced proportions (or the absolute number) of CD19 + CD27 + B cells have already been considered as a main feature of active SLE B cells. 3, 4 However, CD19 + CD27 − B cells also represent a large fraction of memory B cells, and their percentage substantially increased in SLE patients. 4, 5, 6 It was identified that marked B lymphopenia affected CD19 + CD27 − B cells more than CD19 + CD27 + B cells in SLE patients.…”

Section: Discussionmentioning

confidence: 99%

“…3, 4 However, CD19 + CD27 − B cells also represent a large fraction of memory B cells, and their percentage substantially increased in SLE patients. 4, 5, 6 It was identified that marked B lymphopenia affected CD19 + CD27 − B cells more than CD19 + CD27 + B cells in SLE patients. 7 Intriguingly, our results showed the proportion of CD19 + CD27 − B-cell death was significantly increased, whereas the proportion of CD19 + CD27 + B cells was indeed reduced in active SLE patient (Figures 1g and f).…”

Section: Discussionmentioning

confidence: 99%

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Activation-induced necroptosis contributes to B-cell lymphopenia in active systemic lupus erythematosus

et al. 2014

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B-cell abnormality including excessive activation and lymphopenia is a central feature of systemic lupus erythematosus (SLE). Although activation threshold, auto-reaction and death of B cells can be affected by intrinsical and/or external signaling, the underlying mechanisms are unclear. Herein, we demonstrate that co-activation of Toll-like receptor 7 (TLR7) and B-cell receptor (BCR) pathways is a core event for the survival/dead states of B cells in SLE. We found that the mortalities of CD19+CD27- and CD19+IgM+ B-cell subsets were increased in the peripheral blood mononuclear cells (PBMCs) of SLE patients. The gene microarray analysis of CD19+ B cells from active SLE patients showed that the differentially expressed genes were closely correlated to TLR7, BCR, apoptosis, necroptosis and immune pathways. We also found that co-activation of TLR7 and BCR could trigger normal B cells to take on SLE-like B-cell characters including the elevated viability, activation and proliferation in the first 3 days and necroptosis in the later days. Moreover, the necroptotic B cells exhibited mitochondrial dysfunction and hypoxia, along with the elevated expression of necroptosis-related genes, consistent with that in both SLE B-cell microarray and real-time PCR verification. Expectedly, pretreatment with the receptor-interacting protein kinase 1 (RIPK1) inhibitor Necrostatin-1, and not the apoptosis inhibitor zVAD, suppressed B-cell death. Importantly, B cells from additional SLE patients also significantly displayed high expression levels of necroptosis-related genes compared with those from healthy donors. These data indicate that co-activation of TLR7 and BCR pathways can promote B cells to hyperactivation and ultimately necroptosis. Our finding provides a new explanation on B-cell lymphopenia in active SLE patients. These data suggest that extrinsic factors may increase the intrinsical abnormality of B cells in SLE patients.

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“…CD27-IgD-) phenotype and correlate with renal involvement [17,18]. Additionally, several groups reported on marked decline in the frequency of CD27+IgD+ B-cells (NSM) mostly in patients with active disease [18][19][20]. B-cell lymphopenia is another typical feature of SLE, but less is known if it affects all B-cell subsets, and whether it is associated with similar abnormalities in T-cell compartment.…”

Section: Introductionmentioning

confidence: 99%

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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Peripheral B cell abnormalities in patients with systemic lupus erythematosus in quiescent phase: Decreased memory B cells and membrane CD19 expression

Cited by 54 publications

References 51 publications

Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL

Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL

Activation-induced necroptosis contributes to B-cell lymphopenia in active systemic lupus erythematosus

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

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