scholarly journals Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Agata N. Burska ◽  
Laura Hunt ◽  
Marjorie Boissinot ◽  
Rocky Strollo ◽  
Brent J. Ryan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
B Cell ◽  
Rheumatoid Factor ◽  
Posttranslational Modifications ◽  
B Cell Development ◽  
Long Time ◽  
Anticitrullinated Protein Antibodies ◽  
Human B Cell

Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell developmentin vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential.

scholarly journals Differential Regulation of Mouse B Cell Development by Transforming Growth Factor β1

2002 ◽  
Vol 9 (2) ◽  
pp. 86-95 ◽  
Author(s):  
Denise A. Kaminski ◽  
John J. Letterio ◽  
Peter D. Burrows
Keyword(s):  
B Cells ◽  
Growth Factor ◽  
B Cell ◽  
Transforming Growth Factor ◽  
Plasma Cells ◽  
Population Analysis ◽  
Cell Development ◽  
B Cell Development

Transforming growth factor β (TGFβ) can inhibit thein vitroproliferation, survival and differentiation of B cell progenitors, mature B lymphocytes and plasma cells. Here we demonstrate unexpected, age-dependent reductions in the bone marrow (BM) B cell progenitors and immature B cells in TGFβ1-/-mice. To evaluate TGFβ responsiveness during normal B lineage development, cells were cultured in interleukin 7 (IL7)±TGFβ. Picomolar doses of TGFβ1 reduced pro-B cell recoveries at every timepoint. By contrast, the pre-B cells were initially reduced in number, but subsequently increased compared to IL7 alone, resulting in a 4-fold increase in the growth rate for the pre-B cell population. Analysis of purified BM sub-populations indicated that pro-B cells and the earliest BP1-pre-B cells were sensitive to the inhibitory effects of TGFβ1. However, the large BP1+pre-B cells, although initially reduced, were increased in number at days 5 and 7 of culture. These results indicate that TGFβ1 is important for normal B cell developmentin vivo, and that B cell progenitors are differentially affected by the cytokine according to their stage of differentiation.

scholarly journals Ligand-independent Signaling Functions for the B Lymphocyte Antigen Receptor and Their Role in Positive Selection during B Lymphopoiesis

2001 ◽  
Vol 194 (11) ◽  
pp. 1583-1596 ◽  
Author(s):  
Gregory Bannish ◽  
Ezequiel M. Fuentes-Pananá ◽  
John C. Cambier ◽  
Warren S. Pear ◽  
John G. Monroe
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Antigen Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
B Lymphopoiesis ◽  
Biologically Relevant ◽  
Developmental Progression

Signal transduction through the B cell antigen receptor (BCR) is determined by a balance of positive and negative regulators. This balance is shifted by aggregation that results from binding to extracellular ligand. Aggregation of the BCR is necessary for eliciting negative selection or activation by BCR-expressing B cells. However, ligand-independent signaling through intermediate and mature forms of the BCR has been postulated to regulate B cell development and peripheral homeostasis. To address the importance of ligand-independent BCR signaling functions and their regulation during B cell development, we have designed a model that allows us to isolate the basal signaling functions of immunoglobulin (Ig)α/Igβ-containing BCR complexes from those that are dependent upon ligand-mediated aggregation. In vivo, we find that basal signaling is sufficient to facilitate pro-B → pre-B cell transition and to generate immature/mature peripheral B cells. The ability to generate basal signals and to drive developmental progression were both dependent on plasma membrane association of Igα/Igβ complexes and intact immunoregulatory tyrosine activation motifs (ITAM), thereby establishing a correlation between these processes. We believe that these studies are the first to directly demonstrate biologically relevant basal signaling through the BCR where the ability to interact with both conventional as well as nonconventional extracellular ligands is eliminated.

scholarly journals In Vivo Tungsten Exposure Alters B-Cell Development and Increases DNA Damage in Murine Bone Marrow

2012 ◽  
Vol 131 (2) ◽  
pp. 434-446 ◽  
Author(s):  
Alexander D. R. Kelly ◽  
Maryse Lemaire ◽  
Yoon Kow Young ◽  
Jules H. Eustache ◽  
Cynthia Guilbert ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
B Cell ◽  
Cell Development ◽  
B Cell Development ◽  
Murine Bone Marrow

scholarly journals Mutations of the Igβ gene cause agammaglobulinemia in man

2007 ◽  
Vol 204 (9) ◽  
pp. 2047-2051 ◽  
Author(s):  
Simona Ferrari ◽  
Vassilios Lougaris ◽  
Stefano Caraffi ◽  
Roberta Zuntini ◽  
Jianying Yang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Transmembrane Protein ◽  
Serum Levels ◽  
Cell Development ◽  
B Cell Development ◽  
Surrogate Light Chain ◽  
Human B Cell ◽  
Homozygous Nonsense Mutation

Agammaglobulinemia is a rare primary immunodeficiency characterized by an early block of B cell development in the bone marrow, resulting in the absence of peripheral B cells and low/absent immunoglobulin serum levels. So far, mutations in Btk, μ heavy chain, surrogate light chain, Igα, and B cell linker have been found in 85–90% of patients with agammaglobulinemia. We report on the first patient with agammaglobulinemia caused by a homozygous nonsense mutation in Igβ, which is a transmembrane protein that associates with Igα as part of the preBCR complex. Transfection experiments using Drosophila melanogaster S2 Schneider cells showed that the mutant Igβ is no longer able to associate with Igα, and that assembly of the BCR complex on the cell surface is abrogated. The essential role of Igβ for human B cell development was further demonstrated by immunofluorescence analysis of the patient's bone marrow, which showed a complete block of B cell development at the pro-B to preB transition. These results indicate that mutations in Igβ can cause agammaglobulinemia in man.

Antibodies toPorphyromonas gingivalisAre Associated with Anticitrullinated Protein Antibodies in Patients with Rheumatoid Arthritis and Their Relatives

2010 ◽  
Vol 37 (6) ◽  
pp. 1105-1112 ◽  
Author(s):  
CAROL A. HITCHON ◽  
FATIHA CHANDAD ◽  
ELIZABETH D. FERUCCI ◽  
ANNEMIEK WILLEMZE ◽  
ANDREEA IOAN-FACSINAY ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Rheumatoid Factor ◽  
Porphyromonas Gingivalis ◽  
Immune Tolerance ◽  
Oral Hygiene ◽  
Shared Epitope ◽  
Poor Oral Hygiene ◽  
Citrullinated Peptide ◽  
Anticitrullinated Protein Antibodies

Objective.Anticitrullinated protein antibodies (ACPA) are relatively specific for rheumatoid arthritis (RA), and predate disease. The oral pathogenPorphyromonas gingivalismay play a role in breaking immune tolerance to citrullinated antigens. We studied a cohort of patients with RA and their relatives looking for associations between anti-P. gingivalisantibodies and ACPA.Methods.Patients with RA (n = 82) and their relatives (n = 205) from a North American Native (NAN) population were studied, along with 47 NAN and 60 non-NAN controls. IgM and IgA rheumatoid factor (RF) were tested by nephelometry and ELISA. Second-generation anticyclic citrullinated peptide (anti-CCP2) isotypes and IgG anti-P. gingivalislipopolysaccharides were tested by ELISA. HLA-DRB1 typing was performed by sequencing. Oral hygiene and smoking habits were assessed by questionnaires.Results.Autoantibody frequency in patients with RA and relatives: ACPA 91% vs 19%, respectively; IgM RF 82% vs 17%; IgA RF 48% vs 22%. Anti-P. gingivalislevels were higher in patients with RA compared to relatives and controls (p = 0.005) and higher in ACPA-positive patients with RA than in ACPA-negative patients with RA (p = 0.04) and relatives (p < 0.001), but comparable in RF-positive and RF-negative patients and relatives. Poor oral hygiene and smoking were prevalent, but with no clear association with autoantibodies. Relatives with 2 shared-epitope alleles were more likely to be ACPA-positive (OR 2.5, p = 0.02).Conclusion.In a genetically predisposed population of NAN patients with RA and their relatives, anti-P. gingivalisantibodies were associated with ACPA. These findings suggest that immune responses toP. gingivalismay be involved in breaking immune tolerance to citrullinated antigens.

scholarly journals Transitional B Cells in Early Human B Cell Development – Time to Revisit the Paradigm?

2016 ◽  
Vol 7 ◽  
Author(s):  
Victoria G. Martin ◽  
Yu-Chang Bryan Wu ◽  
Catherine L. Townsend ◽  
Grace H. C. Lu ◽  
Joselli Silva O’Hare ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Development Time ◽  
Cell Development ◽  
B Cell Development ◽  
Transitional B Cells ◽  
Early Human ◽  
Human B Cell
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