scholarly journals An apoptosis-dependent checkpoint for autoimmunity in memory B and plasma cells

2020 ◽  
Vol 117 (40) ◽  
pp. 24957-24963 ◽  
Author(s):  
Christian T. Mayer ◽  
Jan P. Nieke ◽  
Anna Gazumyan ◽  
Melissa Cipolla ◽  
Qiao Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Lymphocytes ◽  
Antinuclear Antibody ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Measurable Effect ◽  
Gene Diversification ◽  
Shed Light ◽  
Antibody Gene

B lymphocytes acquire self-reactivity as an unavoidable byproduct of antibody gene diversification in the bone marrow and in germinal centers (GCs). Autoreactive B cells emerging from the bone marrow are silenced in a series of well-defined checkpoints, but less is known about how self-reactivity that develops by somatic mutation in GCs is controlled. Here, we report the existence of an apoptosis-dependent tolerance checkpoint in post-GC B cells. Whereas defective GC B cell apoptosis has no measurable effect on autoantibody development, disruption of post-GC apoptosis results in accumulation of autoreactive memory B cells and plasma cells, antinuclear antibody production, and autoimmunity. The data presented shed light on mechanisms that regulate immune tolerance and the development of autoantibodies.

scholarly journals The Normal Counterpart of IgD Myeloma Cells in Germinal Center Displays Extensively Mutated IgVH Gene, Cμ–Cδ Switch, and λ Light Chain Expression

1998 ◽  
Vol 187 (8) ◽  
pp. 1169-1178 ◽  
Author(s):  
Christophe Arpin ◽  
Odette de Bouteiller ◽  
Diane Razanajaona ◽  
Isabelle Fugier-Vivier ◽  
Francine Brière ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Light Chain ◽  
Germinal Center ◽  
Plasma Cells ◽  
Precursor Cells ◽  
Memory B Cells ◽  
Hematopoietic Stem ◽  
Myeloma Cells ◽  
Λ Light Chain

Human myeloma are incurable hematologic cancers of immunoglobulin-secreting plasma cells in bone marrow. Although malignant plasma cells can be almost eradicated from the patient's bone marrow by chemotherapy, drug-resistant myeloma precursor cells persist in an apparently cryptic compartment. Controversy exists as to whether myeloma precursor cells are hematopoietic stem cells, pre–B cells, germinal center (GC) B cells, circulating memory cells, or plasma blasts. This situation reflects what has been a general problem in cancer research for years: how to compare a tumor with its normal counterpart. Although several studies have demonstrated somatically mutated immunoglobulin variable region genes in multiple myeloma, it is unclear if myeloma cells are derived from GCs or post-GC memory B cells. Immunoglobulin (Ig)D-secreting myeloma have two unique immunoglobulin features, including a biased λ light chain expression and a Cμ–Cδ isotype switch. Using surface markers, we have previously isolated a population of surface IgM−IgD+CD38+ GC B cells that carry the most impressive somatic mutation in their IgV genes. Here we show that this population of GC B cells displays the two molecular features of IgD-secreting myeloma cells: a biased λ light chain expression and a Cμ–Cδ isotype switch. The demonstration of these peculiar GC B cells to differentiate into IgD-secreting plasma cells but not memory B cells both in vivo and in vitro suggests that IgD-secreting plasma and myeloma cells are derived from GCs.

scholarly journals B lymphocytes express and lose syndecan at specific stages of differentiation.

1989 ◽  
Vol 1 (1) ◽  
pp. 27-35 ◽  
Author(s):  
R D Sanderson ◽  
P Lalor ◽  
M Bernfield
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Receptor Expression ◽  
Cell Stage ◽  
Precursor B Cells

Lymphopoietic cells require interactions with bone marrow stroma for normal maturation and show changes in adhesion to matrix during their differentiation. Syndecan, a heparan sulfate-rich integral membrane proteoglycan, functions as a matrix receptor by binding cells to interstitial collagens, fibronectin, and thrombospondin. Therefore, we asked whether syndecan was present on the surface of lymphopoietic cells. In bone marrow, we find syndecan only on precursor B cells. Expression changes with pre-B cell maturation in the marrow and with B-lymphocyte differentiation to plasma cells in interstitial matrices. Syndecan on B cell precursors is more heterogeneous and slightly larger than on plasma cells. Syndecan 1) is lost immediately before maturation and release of B lymphocytes into the circulation, 2) is absent on circulating and peripheral B lymphocytes, and 3) is reexpressed upon their differentiation into immobilized plasma cells. Thus, syndecan is expressed only when and where B lymphocytes associate with extracellular matrix. These results indicate that B cells differentiating in vivo alter their matrix receptor expression and suggest a role for syndecan in B cell stage-specific adhesion.

Phenotypic Analysis of CD19+ Subsets In Monoclonal Gammopathy Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4998-4998
Author(s):  
Lucie Kovarova ◽  
Pavla Zarbochova ◽  
Tamara Varmuzova ◽  
Ivana Buresova ◽  
Karthick Raja Muthu Raja ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Healthy Volunteers ◽  
Peripheral Blood ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Phenotypic Analysis ◽  
Transitional B Cells ◽  
Significant Difference

Abstract Abstract 4998 Background. Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell disorder which can eventually progress into malignant multiple myeloma (MM). Plasma cells (PCs) are the terminal stadium of B cells differentiation, but it is still unclear which population is the source of pathological PCs with malignant transformation and which population is involved in and may give rise to clonogenic myeloma stem cells. Aims. Phenotypic analysis of CD19+ cell subpopulations in monoclonal gammopathy patients and healthy volunteers to asses their frequency and to find differences on cellular level. Methods. Total of 38 samples was analyzed (16 newly diagnosed untreated MM patients, 12 untreated MGUS persons and 10 healthy donors). CD19+ cells were analyzed for surface expression of CD24, CD27, CD38, and IgD by 5-colors immunophenotyping. Subpopulations of pre-plasma cells consist of transitional B cells (CD24+CD38+), naïve B cells (CD38-IgD+), activated B cells (CD38+IgD+), preGC B cells (CD38++IgD+) and memory B cells (CD38-/+IgD-). These were evaluated in whole lysed peripheral blood together with circulating plasmablast/plasma cells (CD38++IgD-). Bone marrow of MGUS and MM patients was analyzed for number of transitional, immature and memory B cells. Results. Flow cytometric analysis shown no statistical difference when compared number of transitional B cells (1.8%; 3.0% and 1.2%) and activated B cells (54.6%; 62.1% and 45.5%) in peripheral blood of healthy volunteers, MGUS and MM patients, respectively. There was found lower number of circulating plasmablast/plasma cells in peripheral blood of healthy volunteers than in MGUS (1.0% vs. 1.7%; p<0.01), but there was no statistically significant difference for MM (1.7%) when compared to others. The highest number of peripheral naive B cells was found in healthy volunteers (21.4%; p<0.001) and the highest number of peripheral memory B cells was found in MM patients (32.9%; p<0.01) when compared to other groups. There was found also higher number of peripheral preGC B cells in MGUS and MM patients (2.7% vs. 1.6% vs. 1.3%; p<0.05) than in healthy volunteers, respectively. Although numbers of transitional and immature B cells in bone marrow were different for MGUS and MM, the only statistically significant difference was found in number of memory B cells (25.4% for MGUS vs. 11.9% for MM; p<0.01). Summary/Conclusions. Our result showed differences in CD19+ subsets when compared peripheral blood of healthy volunteers and monoclonal gammopathy patients as well as in bone marrow of monoclonal gammopathy group. These differences could be a sign of ongoing changes in B cells of monoclonal gammopathy patients. Further analysis will be also focused on changes at DNA level to confirm clonality of selected subpopulations and to find possible myeloma stem cells source. Supported by GACR 301/09/P457, GACR GAP304/10/1395, MSMT LC06027, MSM0021622434, IGA 10408-3, IGA 10406-3. Disclosures: Hajek: Janssen-Cilag: Honoraria; Celgene: Honoraria; Merck, Sharp, and Dohme: Honoraria.

Flow Cytometry Primary 10 Colours Panel for Chronic Lympho Proliferative Diseases Diagnosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5190-5190
Author(s):  
Jonathan Brauner ◽  
Ingrid Beukinga ◽  
Zoulikha Amraoui ◽  
Zaina Kassengera ◽  
Michel Toungouz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Lymphocytes ◽  
Plasma Cells ◽  
Cell Lymphoma ◽  
Cd10 Expression ◽  
Complete Characterisation

Abstract Abstract 5190 Objectives: Definition of the primary antibodies panel for 10 colours flow cytometry able to describe normal and clonal T, B lymphocytes and plamocytes in blood and bone marrow. Once clonalities are detected, the complete characterisation of Chronic Lymphoproliferative Diseases (CLPD) is supported by secondary panels chosen based on the results of CD5/CD10 expression for clonal B lymphocytes, CD27/CD38 for plasmatocytes and CD3/CD27 for clonal T cells. Materials and Methods: Blood and bone marrow of patients (N=50) with CLPD (mainly B-CLL). Samples are enumerated by haematology analyzer DxH 800 then 106 cells are washed three times, stained with the antibodies combination and red blood cells lysed with Versalyse (TM. Beckman Coulter). The samples were analysed on a 10 colours Navios flow cytometer (Beckman Coulter Fullerton, CA). The staining panel consists of 14 antibodies (CD45, CD8, CD4, CD5, CD3, CD19, CD38, λ, κ, CD23, CD5, CD10, CD14, CD27) conjugated with 10 different fluorochromes. The fixed gating strategy allows linking Navios analysis software to the middleware Remisol which drives the choice of the secondary panel. In some cases a third tube is performed for Ki67 or Zap-70 intra-cytoplasmic staining. Results: Monocytes are removed on the basis of their CD14/CD4 expression. B lymphocytes are CD19 positive. Normal naïve/memory B cells, hematogones and plasma cells are defined by their CD27, CD10 and CD38 expression. Eventual monoclonality is sought by analysis of the distribution of Kappa and Lambda light chains. A first classification of B cell lymphoma is achieved with the CD5 and CD10 expression of the clone (CD5+/CD10−: B-CLL MCL and few MZL, CD5−/CD10−: MZL and related, CD5−/CD10+ DLBCL and FL). Analysis of CD27, CD20 and CD23 expression allows discriminating between CD5+/CD10- lymphomas. All the 50 samples were correctly detected as CLPD and the automated Remisol choice of the second panel fit to the final diagnosis of all the cases of this small series. T lymphocytes are defined by their CD3 and CD5 expression. The analysis of CD4/CD8 balance and CD27/CD5 distribution are first line test when T cell clonality is suspected. There is a special gating to detect CD3-CD4+ T cell lymphoma and double negativity of CD4 and CD8 is a surrogate marker for gamma/delta T cells. NK cells are mentioned as not-T not-B lymphocytes, without specific staining. Conclusion/Discussion:This 10 colours 14 antibodies panel allows describing in one tube normal T and B cells, hematogones, memory and naives B cells plasma cells and detects T and B clonalities. This panel follows a similar logic than the Euroflow LST tube but with 10 colours and with Beckman Coulter's technology and antibodies. Moreover, this combination helps discriminating rapidly the CD5+/CD10- lymphomas while the complete characterisation of CD5 negative lymphomas only require less than 6 antibodies second tube. This is a paperless (all the process is driven and controlled by Remisol), fast and inexpensive diagnostic approach (always less than 20 antibodies required). Disclosures: Pradier: Beckman Coulter: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Abnormal Microenvironment of Bone Marrow B Lymphocytes in Patients with Primary Immune Thrombocytopenia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3759-3759
Author(s):  
Tianshu Yu ◽  
Ming Hou ◽  
Xinguang Liu ◽  
Panpan Han
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Lymphocytes ◽  
Chemokine Receptors ◽  
Immune Thrombocytopenia ◽  
Plasma Cells ◽  
Healthy Donors ◽  
Significant Difference ◽  
Primary Immune Thrombocytopenia ◽  
Development And Differentiation

Abstract BACKGROUNDS: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by peripheral blood platelet count<100x10^9/L and increased risk of bleeding, but its exact pathogenesis remains unclear. Previous researches mostly emphasized on periphral blood, in order to elucidate the pathogenesis and provide new strategies for treatment, a series of studies about bone marrow B cells were carried out in our investigation. METHODS: 5ml bone marrow blood samples from 11 newly diagnosed ITP patients and 7 allo-HSCT healthy donors were collected into heparin anticoagulant tubes , bone marrow mononuclear cells (BMMCs) were separated with Ficoll density gradient-centrifugation in two hours. Different subsets of B lymphocytes were determined by multicolor flow cytometry including naive B cells, total memory B cells , plasma cells and regulatory B cells (Bregs) ,as well as some chemokine receptors of B cells (CXCR5, BAFFR, BCMA, TACI) . RNA were extracted from BMMCs using Trizol reagent, transcription factors related to development and differentiation of B cells (PRDM1, Pax5, IRF-4, XBP1) were detected by real-time PCR. RESULTS: The percentage of B cells (CD19+) in bone marrow lymphocytes in ITP patients was significantly lower than that in healthy donors (6.16±0.74% vs. 17.28±2.43%, P < 0.0001). The proportion of naive B (CD19+CD27-) in B cells was also lower compared with normal controls (59.11±7.60% vs. 81.58±4.00%, P=0.041), and the proportion of memory B (CD19+CD27+) was higher(40.17±7.67% vs. 18.01±3.89%, P=0.045),but there was no significant difference in plasma cells (CD19-CD138+). Besides,there was a decrease of Breg (CD19+CD24highCD38high) in ITP patients compared with healthy donors (20.33±5.05% vs. 57.98±9.76% , P = 0.008), and its percentage of total lymphocytes was also significantly lower unsurprisingly (1.38±0.38% vs. 12.23±2.88%, P < 0.001). The level of BAFFR in mature B cells was elevated in ITP patients (80.72±4.53% vs. 45.81±8.49%, P = 0.002). However, no significant difference was observed in other three chemokine receptors. All four Transcription factors related to B cell development and differentiation was not found to be significantly different between ITP patients and healthy controls. CONCLUSIONS: Our results showed that memory B cells which represent the active form were increased, and Bregs which mediate immune tolerance were much more decreased in ITP patients. As BAFFR is the only specific receptor of B cell activating factor(BAFF), its elevated expression suggested the BAFF-BAFFR system enhanced chemotactic function of B cells in ITP patients. All those results indicated that the bone marrow B cells in patients with ITP were in a state of immune overstimulation, this may potentially constitute a novel therapeutic target. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Multiple Myeloma Cancer Stem Cell Animal Model.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1848-1848
Author(s):  
Christina C.N. Wu ◽  
Daniel Jacob Goff ◽  
Wenxue Ma ◽  
Heather Leu ◽  
Thomas A. Lane ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cells ◽  
Plasma Cells ◽  
Memory B Cells ◽  
The Self ◽  
High Dose ◽  
Self Renewal ◽  
Immunomagnetic Bead

Abstract Abstract 1848 Poster Board I-874 Multiple myeloma (MM) is the second most common hematologic malignancy and characterized by clonal proliferation of CD138+ bone marrow plasma cells. Despite various treatment options few patients with MM have been cured. Furthermore, high relapse rates and recent evidence from xenogeneic transplantation models and primary MM marrow samples indicate that a rare population of cells or MM cancer stem cells (MM CSCs) within the marrow regenerates itself and may be responsible for drug resistance. These MM CSCs are phenotypically similar to memory B cells (CD138- CD34-CD19+) but differ in that they have the capacity to regenerate themselves or self-renewal. However, most of the reports on MM CSC animal models are established in NOD/SCID mice that require a larger number (1 – 10 × 106) of bead sorted cells for each animal. In addition, the latency of MM induction (4 – 6 months) in NOD/SCID mouse models and lack of in vivo tracking of the malignant clone preclude robust pre-clinical testing of novel therapeutic strategies that target MM CSC. Mononuclear cells were isolated from autologous mobilized peripheral blood of at least four primary MM patients after Ficoll gradient centrifugation followed by immunomagnetic bead depletion of CD34+ and CD138+ cells and/or further sorted using a FACSAria. The CD138-CD34- population was transduced with lentiviral luciferase GFP (GLF) and transplanted (10,000 to 106 cells per mouse) intrahepatically into neonatal RAG2-/- gamma chain-/- (RAG2-/-gc-/-) mice. Engraftment was compared to mice transplanted with either CD34+ or CD138+ cells. Mice were imaged with an in vivo imaging system (IVIS) to detect bioluminescent engraftment. Results showed that a relatively rare CD138- CD27+ population, resembling memory B cells (∼1.2%), persists in MM autografts and can engraft immunocompromised mice more rapidly and effectively than the CD138+ (Lin+) population of mature plasma cells. This data supports the persistence of CSCs despite high dose chemotherapy further underscoring the need for CSC targeted therapy. Bioluminescence was detected in live mice transplanted with as little as 60,000 cells of CD138- CD34- population and as soon as 4 weeks after transplantation. FACS analysis of these mice demonstrated successful engraftment with the presence of CD45+ and CD138+ population in bone marrow, spleen and liver and bioluminescence was also detected in the secondary transplantation of cells from MMCSC primary engraftment demonstrating the self-renewal capacity of this rare CD138- CD27+ population. Our results suggest that by utilizing a lentiviral GFP-luciferase system in a highly immunocompromised mouse strain fewer cells will be required to monitor MM engraftment and perhaps hasten disease development. Further studies to confirm the expression of selected IgG genes from myeloma cells and to characterize the self-renewal capacity with genes involved in developmental signaling such as sonic hedgehog and wnt pathways are underway. Disclosures: Goff: Coronado Biosciences: Research Funding.

scholarly journals Evidence for a bone marrow B cell transcribing malignant plasma cell VDJ joined to C mu sequence in immunoglobulin (IgG)- and IgA-secreting multiple myelomas.

1993 ◽  
Vol 178 (3) ◽  
pp. 1091-1096 ◽  
Author(s):  
P Corradini ◽  
M Boccadoro ◽  
C Voena ◽  
A Pileri
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Bone Marrow Cells ◽  
Indirect Evidence ◽  
Specific Marker

Multiple myeloma is a B cell malignancy characterized by the expansion of plasma cells producing monoclonal immunoglobulins (Ig). It has been regarded as a tumor arising at the B, pre-B lymphocyte, or even stem cell level. Precursor cells are presumed to proliferate and differentiate giving rise to the plasma cell clonal expansion. Antigenic features and specific Ig gene rearrangement shared by B lymphocytes and myeloma cells have supported this hypothesis. However, the existence of such a precursor is based upon indirect evidence and is still an open question. During differentiation, B cells rearrange variable (V) regions of Ig heavy chain genes, providing a specific marker of clonality. Using an anchor polymerase chain reaction assay, these rearranged regions from five patients with multiple myeloma were cloned and sequenced. The switch of the Ig constant (C) region was used to define the B cell differentiation stage: V regions are linked to C mu genes in pre-B and B lymphocytes (pre-switch B cells), but to C gamma or C alpha in post-switch B lymphocytes and plasma cells (post-switch B cells). Analysis of bone marrow cells at diagnosis revealed the presence of pre-switch B cells bearing plasma cell V regions still joined to the C mu gene. These cells were not identified in peripheral blood, where tumor post-switch B cells were detected. These pre-switch B cells may be regarded as potential myeloma cell precursors.

Circulating B Lymphocytes from Patients with Multiple Myeloma Harbour T(4;14) Translocations and Chromosome 13 Deletions.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 500-500 ◽  
Author(s):  
Carina Debes-Marun ◽  
Andrew R. Belch ◽  
Linda M. Pilarski
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cells ◽  
B Lymphocytes ◽  
Plasma Cells ◽  
Chromosomal Abnormalities ◽  
Minority Population ◽  
Polymorphonuclear Cells ◽  
Chromosome 13 ◽  
Healthy Donors

Abstract Multiple Myeloma (MM) is clinically characterized by accumulations of plasma cells in the bone marrow (BM). We have identified drug resistant clonotypic B lymphocytes in the peripheral blood of MM patients that have malignant characteristics and the ability to xenograft MM to immunodeficient mice. Using an automated scanning system (Bioview Duet), for blood samples from 72 MM patients, we scanned cytospin slides stained with May-Grunwald Giemsa to identify lymphocytes and determine whether they have the same chromosomal abnormalities that characterize autologous plasma cells. The location on the slide of each morphologically identified cell is recorded during an initial scan, followed by FISH, and examination of the same cells for genetic abnormalities. For this study, we chose probes to detect 1) deletion of chromosome 13 using D13S319 (Vysis), and 2) the t(4;14)(p16;q32) translocation using a dual fusion probe (Vysis). Both abnormalities correlate with adverse prognosis. Lymphocytes from PBMC of healthy donors show 2.8+/−1% of lymphocytes with Ch13 deletion, and less than 1% with t(4;14). An MM PBMC sample was considered to have lymphocyte abnormalities if it scored above a cut off value of 10% for Ch13 deletions and 2% for t(4;14), this is likely to underestimate the extent of chromosomal abnormalities in MM B cells. The number of abnormal lymphocytes in MM PBMC is sufficiently large, and the number of abnormal cells in comparable populations from healthy donors is sufficiently small, that we are readily able to detect significantly increased numbers of abnormal lymphocytes in MM PBMC. We found that peripheral lymphocytes from 19/60 (32%) MM patients have Ch13 deletion (27%) and/or t(4;14) (26%); for those patients with an available BM sample, these same abnormalities were found in their BM plasma cells. Interestingly, intraclonal heterogeneity is apparent in malignant cells from a t(4;14) patient; these plasma cells include a minority population with apparent Ch14 monosomy (23%) and a major population having two copies of Ch14 (77%). This was internally controlled in that for both populations, the plasma cells have two copies of the fused t(4;14) chromosome, and the polymorphonuclear cells on the same slide were normal. One MM patient had Ch13 deletion in 60% of lymphocytes from PBMC, consistent with the 63% of BM plasma cells from this same patient showing Ch13 deletion. For another MM patient known to be t(4;14)+, sorted sIgM+ B cells were analyzed and found to include a small subset with t(4;14) translocations. For 2/6 MM PBMC, abnormalities in Ch19 were detectable in 25–37% of lymphocytes. For mobilized blood autografts, preliminary data indicates the presence of lymphocytic cells with detectable Ch13 deletion. By performing FISH after immunostaining with anti-CD20 of PBMC from MM patients whose bone marrow plasma cells had Ch13 deletion/monosomy, we detected chromosomal abnormalities in CD20+ B cells from MM blood. No abnormalities were detected for CD20+ B cells from healthy donors. In the context of our previous work, this analysis demonstrates that two molecular signatures of MM, clonotypic IgH gene rearrangements and, as reported here, prognostically important chromosomal abnormalities are found among circulating CD20+ B cells from the blood of patients with MM. This work confirms that the MM clone includes circulating B lymphocytes harbouring chromosomal deletions or IgH switch region translocations known to be clinically significant in MM, further implicating them as a source of relapse.

scholarly journals Maintenance of Anti-Sm/RNP Autoantibody Production by Plasma Cells Residing in Ectopic Lymphoid Tissue and Bone Marrow Memory B Cells

2013 ◽  
Vol 190 (8) ◽  
pp. 3916-3927 ◽  
Author(s):  
Jason S. Weinstein ◽  
Matthew J. Delano ◽  
Yuan Xu ◽  
Kindra M. Kelly-Scumpia ◽  
Dina C. Nacionales ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Lymphoid Tissue ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Autoantibody Production
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