scholarly journals Maintenance of Long-Lived Plasma Cells and Serological Memory Despite Mature and Memory B Cell Depletion during CD20 Immunotherapy in Mice

2007 ◽  
Vol 180 (1) ◽  
pp. 361-371 ◽  
Author(s):  
David J. DiLillo ◽  
Yasuhito Hamaguchi ◽  
Yoshihiro Ueda ◽  
Kaiyong Yang ◽  
Junji Uchida ◽  
...  
Keyword(s):  
B Cell ◽  
Plasma Cells ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Memory B Cell

scholarly journals B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells

2012 ◽  
Vol 123 (1) ◽  
pp. 432-442 ◽  
Author(s):  
Matthieu Mahévas ◽  
Pauline Patin ◽  
François Huetz ◽  
Marc Descatoire ◽  
Nicolas Cagnard ◽  
...  
Keyword(s):  
B Cell ◽  
Immune Thrombocytopenia ◽  
Plasma Cells ◽  
Cell Depletion ◽  
B Cell Depletion

Steady-state generation of mucosal IgA+ plasmablasts is not abrogated by B-cell depletion therapy with rituximab

Blood ◽  
2010 ◽  
Vol 116 (24) ◽  
pp. 5181-5190 ◽  
Author(s):  
Henrik E. Mei ◽  
Daniela Frölich ◽  
Claudia Giesecke ◽  
Christoph Loddenkemper ◽  
Karin Reiter ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Steady State ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Ki 67

AbstractThe anti-CD20 antibody rituximab depletes human B cells from peripheral blood, but it remains controversial to what extent tissue-resident B cells are affected. In representative patients with rheumatoid arthritis, we here demonstrate that recently activated presumably short-lived plasmablasts expressing HLA-DRhigh and Ki-67 continuously circulate in peripheral blood after B-cell depletion by rituximab at 26%-119% of their initial numbers. They circulate independent of splenectomy, express immunoglobulin A (IgA), β7 integrin, and C-C motif receptor 10 (CCR10) and migrate along CCL28 gradients in vitro, suggesting their mucosal origin. These plasmablasts express somatically hypermutated VH gene rearrangements and spontaneously secrete IgA, exhibiting binding to microbial antigens. Notably, IgA+ plasmablasts and plasma cells were identified in the lamina propria of patients treated with rituximab during peripheral B-cell depletion. Although a relation of these “steady state”–like plasmablasts with rheumatoid arthritis activity could not be found, their persistence during B-cell depletion indicates that their precursors, that is, B cells resident in the mucosa are not deleted by this treatment. These data suggest that a population of mucosal B cells is self-sufficient in adult humans and not replenished by CD20+ B cells immigrating from blood, lymphoid tissue, or bone marrow, that is, B cells depleted by rituximab.

scholarly journals A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow

Blood ◽  
2015 ◽  
Vol 125 (11) ◽  
pp. 1739-1748 ◽  
Author(s):  
Henrik E. Mei ◽  
Ina Wirries ◽  
Daniela Frölich ◽  
Mikael Brisslert ◽  
Claudia Giesecke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
B Cell ◽  
Plasma Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Healthy Human ◽  
Key Points

Key Points Healthy human BM is enriched for PC lacking CD19 that express a prosurvival and distinctly mature phenotype. CD19− PC resist mobilization into blood during immune responses after vaccination as well as B-cell depletion with rituximab.

MO251HIGHLY SENSITIVE FLOW CYTOMETRIC DETECTION OF RESIDUAL B-CELLS AFTER RITUXIMAB IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS PATIENTS*

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y K O Teng ◽  
L Van Dam ◽  
Jelle Oskam ◽  
S W A Kamerling ◽  
E J Arends ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
B Cells ◽  
B Cell ◽  
Mononuclear Cells ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Peripheral Blood Mononuclear

Abstract Background and Aims B-cell depletion with rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. Nevertheless, relapses are frequent after RTX, often preceded by B-cell repopulation suggesting that residual autoreactive B-cells persist despite therapy. Therefore, this study aimed to identify minimal residual autoimmunity (MRA) in the B-cell compartment of AAV patients treated with RTX. Method EuroFlow-based highly-sensitive flow cytometry (HSFC) was employed to study B-cell and plasma cell (PC) subsets in-depth in AAV patients before and after RTX treatment. Additionally, peripheral blood mononuclear cells (PBMCs) of these RTX-treated AAV patients were cultured and in vitro stimulated with CpG, IL-2, and IL-21 to induce antibody-secreting cells (ASC). (ANCA)-IgG was measured in these supernatants by ELISA. Results By employing EuroFlow-based HSFC, we detected circulating CD19+ B-cells at all timepoints after RTX treatment, in contrast to conventional low-sensitive flow cytometry. Pre-germinal center (Pre-GC) B-cells, memory B-cells and CD20+CD138− plasmablasts (PBs) were rapidly and strongly reduced, while CD20−CD138− PrePC and CD20-CD138+ mature (m)PCs were reduced slower and remained detectable. Both memory B-cells and CD20− PCs remained detectable after RTX. Serum ANCA-IgG decreased significantly upon RTX. Changes in ANCA levels strongly correlated with changes in naive, switched CD27+ and CD27− (double-negative) memory B-cells, but not with plasma cells. Lastly, we demonstrated in vitro ANCA production by AAV PBMCs, 24 and 48 weeks after RTX treatment reflecting MRA in the memory compartment of AAV patients. Conclusion We demonstrated that RTX induced strong reductions in circulating B-cells, but never resulted in complete B-cell depletion. Despite strongly reduced B-cell numbers after RTX, ANCA-specific memory B-cells were still detectable in AAV patients. Thus, MRA is identifiable in AAV and can provide a potential novel approach in personalizing RTX treatment in AAV patients.

Memory B-cell depletion is a feature of HIV-2 infection even in the absence of detectable viremia

AIDS ◽  
2012 ◽  
Vol 26 (13) ◽  
pp. 1607-1617 ◽  
Author(s):  
Rita Tendeiro ◽  
Sofia Fernandes ◽  
Russell B. Foxall ◽  
José M. Marcelino ◽  
Nuno Taveira ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Memory B Cell

scholarly journals BAFF and CD4+ T cells are major survival factors for long-lived splenic plasma cells in a B-cell–depletion context

Blood ◽  
2018 ◽  
Vol 131 (14) ◽  
pp. 1545-1555 ◽  
Author(s):  
Lan-Huong Thai ◽  
Simon Le Gallou ◽  
Ailsa Robbins ◽  
Etienne Crickx ◽  
Tatiana Fadeev ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Plasma Cells ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Survival Factors ◽  
Key Points ◽  
Anti Cd20

Key Points Modification of the splenic microenvironment induced by B-cell depletion creates a dependence of PCs on BAFF and CD4+ T cells. Combining anti-CD20 and anti-BAFF reduces the number of splenic PCs, opening therapeutic perspectives for antibody-mediated cytopenia.

scholarly journals Bortezomib Treatment for Refractory PLA2R-Positive Membranous Nephropathy

2021 ◽  
Vol 1 (1) ◽  
pp. 40-43
Author(s):  
Abdallah S. Geara ◽  
Vijay Bhoj ◽  
Jonathan J. Hogan
Keyword(s):  
B Cell ◽  
Membranous Nephropathy ◽  
Plasma Cells ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Case Presentation ◽  
Bortezomib Treatment ◽  
First Line Therapy ◽  
Measurable Serum ◽  
History Of

<b><i>Introduction:</i></b> B-cell depletion has been shown to be an effective strategy for the majority of patients with membranous nephropathy (MN), and in PLA2R-positive MN, immunologic remission (improvement or elimination of measurable serum anti-PLA2R antibodies) precedes renal remission. Yet, cases exist of patients who do not achieve immunologic remission despite achieving peripheral B-cell depletion. This has led to the hypothesis that some patients have plasma cells that are responsible for producing anti-PLA2R antibodies. <b><i>Case Presentation:</i></b> A 66-year-old man with a past medical history of hypertension, hyperlipidemia, and cerebrovascular disease presented with nephrotic syndrome and was diagnosed with PLA2R-positive MN on kidney biopsy. He was refractory to multiple therapies including tacrolimus, and was resistant to rituximab despite having achieved B-cell depletion. He also did not enter into remission with plasmapharesis and cyclophosphamide. He then achieved immediate immunologic remission after treatment with the proteasome inhibitor bortezomib, which is used as first-line therapy for multiple myeloma. <b><i>Discussion/Conclusion:</i></b> This case suggests that considering the source of PLA2R antibody production could lead to individualized and targeted therapies for MN.

Sign in / Sign up

Export Citation Format

Share Document