scholarly journals Marginal zone B cells are naturally reactive to collagen type II and are involved in the initiation of the immune response in collagen-induced arthritis

2011 ◽  
Vol 8 (4) ◽  
pp. 296-304 ◽  
Author(s):  
Cecilia Carnrot ◽  
Kajsa E Prokopec ◽  
Kristina Råsbo ◽  
Mikael CI Karlsson ◽  
Sandra Kleinau
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Marginal Zone ◽  
Collagen Type ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Collagen Induced Arthritis ◽  
Marginal Zone B Cells

scholarly journals Morphologic and Functional Effects of Gamma Secretase Inhibition on Splenic Marginal Zone B Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Maria Cristina de Vera Mudry ◽  
Franziska Regenass-Lechner ◽  
Laurence Ozmen ◽  
Bernd Altmann ◽  
Matthias Festag ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
B Cell ◽  
Marginal Zone ◽  
Nuclear Translocation ◽  
Recovery Period ◽  
Functional Characterization ◽  
Notch Receptor ◽  
Marginal Zone B Cells ◽  
Cell Fate Decisions

Theγ-secretase complex is a promising target in Alzheimer’s disease because of its role in the amyloidogenic processing ofβ-amyloid precursor protein. This enzyme also catalyzes the cleavage of Notch receptor, resulting in the nuclear translocation of intracellular Notch where it modulates gene transcription. Notch signaling is essential in cell fate decisions during embryogenesis, neuronal differentiation, hematopoiesis, and development of T and B cells, including splenic marginal zone (MZ) B cells. This B cell compartment participates in the early phases of the immune response to blood-borne bacteria and viruses. Chronic treatment with the oralγ-secretase inhibitor RO4929097 resulted in dose-dependent decreased cellularity (atrophy) of the MZ of rats and mice. Significant decreases in relative MZ B-cell numbers of RO4929097-treated animals were confirmed by flow cytometry. Numbers of MZ B cells reverted to normal after a sufficient RO4929097-free recovery period. Functional characterization of the immune response in relation to RO4929097-related MZ B cell decrease was assessed in mice vaccinated with inactivated vesicular stomatitis virus (VSV). Compared with the immunosuppressant cyclosporin A, RO4929097 caused only mild and reversible delayed early neutralizing IgM and IgG responses to VSV. Thus, the functional consequence of MZ B cell decrease on host defense is comparatively mild.

scholarly journals Visualization and phenotyping of pro-inflammatory antigen-specific T cells during collagen induced arthritis in a mouse with a fixed collagen type II specific transgenic TCR beta chain

2010 ◽  
Vol 12 (4) ◽  
pp. R155 ◽  
Author(s):  
Patrick Merky ◽  
Tsvetelina Batsalova ◽  
Robert Bockermann ◽  
Balik Dzhambazov ◽  
Bettina Sehnert ◽  
...  
Keyword(s):  
T Cells ◽  
Collagen Type ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Beta Chain ◽  
Collagen Induced Arthritis

scholarly journals Humoral immune response to citrullinated collagen type II determinants in early rheumatoid arthritis

2005 ◽  
Vol 35 (5) ◽  
pp. 1643-1652 ◽  
Author(s):  
Harald Burkhardt ◽  
Bettina Sehnert ◽  
Robert Bockermann ◽  
Åke Engström ◽  
Jochen R. Kalden ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
Early Rheumatoid Arthritis ◽  
Humoral Immune Response ◽  
Collagen Type ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Humoral Immune

The Marginal Zone B Cells have an Increased Antibody Expression in Mice with Collagen-induced Arthritis

2009 ◽  
Vol 16 (1) ◽  
pp. 23
Author(s):  
Yun Ju Woo ◽  
Jun Ki Min ◽  
Mi-La Cho ◽  
Young Joo Kim ◽  
Joo Yeon Jhun ◽  
...  
Keyword(s):  
B Cells ◽  
Marginal Zone ◽  
Collagen Induced Arthritis ◽  
Marginal Zone B Cells ◽  
Antibody Expression

scholarly journals Extra-Splenic Role of B Cell Activating Factor Blockade in Prevention of Factor VIII Inhibitors

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1025-1025
Author(s):  
Bhavya S Doshi ◽  
Mostafa A Shaheen ◽  
Juliana C Small ◽  
Paris Margaritis ◽  
Valder R Arruda
Keyword(s):  
Immune Response ◽  
B Cells ◽  
B Cell ◽  
Marginal Zone ◽  
High Titer ◽  
Combined Therapy ◽  
Antibody Therapy ◽  
Marginal Zone B Cells ◽  
Fviii Inhibitor

Abstract The development of neutralizing antibodies (inhibitors) to factor VIII (FVIII) remains the most challenging complication of protein-based replacement therapy in hemophilia A (HA). Elevated levels of the B cell survival cytokine B cell activating factor (BAFF) are associated with inhibitors in HA patients and BAFF levels decrease with successful immune tolerance induction (Doshi BS et al, J Clin Invest 2021). In HA mice, localization of labeled FVIII to the spleen and subsequent depletion of splenic leukocytes has been shown to reduce and/or temporarily prevent FVIII inhibitors. In contrast, transient depletion of BAFF prevented inhibitors upfront and promoted long-term tolerance to FVIII in HA mice. Given BAFF's ability to modulate B cell pools in secondary lymphoid organs, here we compared the splenic versus extra-splenic role of BAFF in regulating the FVIII immune response in order to localize its mechanism of action. As BAFF could regulate survival of innate-like splenic-resident marginal zone B cells, initial experiments compared depletion of BAFF or marginal zone B cells in HA mice and showed more complete inhibitor prevention with BAFF depletion (median 0 vs 16.9 Bethesda Units [BU]/ml, respectively, p < 0.01). These data supported our hypothesis that BAFF's regulatory effect is not solely reliant on its modulation of the splenic-resident marginal zone B cell compartment in HA mice. To further understand the extra-splenic role of BAFF in FVIII immunogenicity, wild-type (WT) or severe HA mice (with F8 exon 16 knockout) on the C57Bl/6 background, were treated according to three groups (n=9-11/group): 1) sham controls, 2) splenectomy alone, and 3) anti-BAFF monoclonal antibody (2mg/kg IP once) 4 days prior to splenectomy ("combined therapy"). Following splenectomy, mice were injected with recombinant full length human FVIII at 80 IU/kg weekly for six weeks. Bethesda titers were measured one week following the final immunization. In order to provide hemostasis in HA mice without FVIII exposure prior to splenectomy, mice were given liver-directed gene therapy with AAV8-mFVIIa at 5e11 vg/mouse two weeks prior to splenectomy. Circulating mFVIIa levels of 5.8 ± 2.4 ug/ml at day 10 were observed. These levels normalized hemostasis allowing successful splenectomy in 85% of animals, which is similar to our experience in WT mice. In the combined therapy group, only a single HA mouse developed a high titer inhibitor (7.4 BU/ml) and no WT mice developed high titer inhibitors. As the presence of endogenous FVIII antigen in WT mice does not seem to significantly alter BAFF's role in preventing the alloantibody response to xenoantigen (human FVIII protein), data for WT and HA mice were combined for analysis. Although splenectomy decreased inhibitors titers compared to sham controls (23.1 vs 78.7 BU/ml), the addition of anti-BAFF antibody therapy to splenectomy significantly reduced the risk of high titer inhibitors (RR 0.15, 95% CI 0.02-0.66, p < 0.01). The median Bethesda titer in HA and WT splenectomized mice was 23.1 (0-139.4) versus 0 (0-7.4) with addition of BAFF antibody therapy. Of note, inhibitor prevention with combination splenectomy and anti-BAFF antibody therapy seen here is similar to our prior data using just anti-BAFF antibody monotherapy for FVIII inhibitor prevention in HA mice (RR 0.23, 95% CI 0.08-0.57) suggesting that splenectomy does not significantly improve FVIII inhibitor prevention in the setting of BAFF inhibition. Our data, using a challenging HA mouse model, suggest that anti-BAFF therapy may prevent FVIII inhibitors by inhibiting BAFF's function in non-splenic lymphoid compartments. As certain B cell subtypes, including marginal zone B cells, reside in non-splenic compartments in humans, our model mimics the anticipated human immune response to FVIII. Ongoing investigations into the B and T cell compartments in lymph nodes and bone marrow will provide further insights into the location of BAFF's regulatory role in the FVIII immune response and may provide insights into potential alternative pathways in the initial FVIII immune response. Disclosures Doshi: Janssen: Consultancy; Spark Therapeutics: Speakers Bureau.

Low affinity antibodies against collagen type II are associated with pathology in collagen-induced arthritis in mice

1990 ◽  
Vol 3 (6) ◽  
pp. 643-657 ◽  
Author(s):  
N STAINES ◽  
T EKONG ◽  
H THOMPSON ◽  
A ISAACS ◽  
B LORYMAN ◽  
...  
Keyword(s):  
Collagen Type ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Collagen Induced Arthritis
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