B Cells and Immunological Tolerance

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (31 August 2013) | Viewed by 87976

Special Issue Editor


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Guest Editor
Division of Pediatric Research Center, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030, USA
Interests: immunity; autoimmunity; tolerance; tregs; regulatory T cells; bregs; B cells; autoantibodies; immune regulation

Special Issue Information

Dear Colleagues,

In this special issue on B cells and immunological tolerance, we will offer an updated knowledge and new perspectives on the multitude of interactions between the B cells and their environment in order to build a fortress against invaders and peace among the citizens. Any perturbations in this harmony and fortitude within the B cells or their communications among different cells can weaken immunity and increase susceptibility to autoimmunity and allergy. As an integral part of the humoral immunity, the B cells play a vital component in the host defense against various microbes, viruses, fungi and toxins. Their antibodies are the missiles and satellites that provide this protection by directly targeting their enemies and communicating between innate and adaptive immunity to amplify their attack. A stringent control on the factories of the B cells is critical to prevent erroneous manufacturing of these antibodies, which could result in off-target injuries to the host.
In the last decade and more recently, we have gained tremendous insights into their machinery, alliances and regulation. They can produce a variety of cytokines to orchestrate the efficiency of other effector cells. They can be regulated and instructed by various cells including follicular helper T cells (Tfh), follicular regulatory T cells (Tfr) and regulatory T cells (Tregs). Their equilibrium between effective immunity and excessive inflammation in order to maintain immunological tolerance also depends on a unique B cell subset called regulatory B cells (Bregs). Through better understanding of these processes and intricate networks, we are able to develop preventative strategies and curative therapies to enhance immunity and eliminate allergic and autoimmune diseases. To put everything into perspective, this special issue will provide a concise review on the machinery and various interactions of B cells with their environment including platelets, Tregs, Tfh, Tfr, Bregs and probiotics that are necessary to maintain immune homeostasis and a balance between immunity and immunological tolerance.

Dr. Dat Q. Tran
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibodies is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • allergy
  • autoimmunity
  • B cells
  • antibodies
  • autoantibodies
  • regulatory B cells (Bregs)
  • regulatory T cells (Tregs)
  • follicular helper T cells (Tfh)
  • follicular regulatory T cells (Tfr)
  • probiotics
  • platelets
  • hemophilia
  • multiple sclerosis
  • cytokines
  • IL10
  • TGFbeta
  • apoptosis
  • anergy
  • tolerance
  • immunoglobulins

Published Papers (7 papers)

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Review

410 KiB  
Review
Role of B Cells in Breaking and Maintaining Tolerance to Clotting Factor VIII in Congenital and Acquired Hemophilia A
by Amanda M. Actor, Claire K. Holley and Keri Csencsits-Smith
Antibodies 2014, 3(2), 192-204; https://doi.org/10.3390/antib3020192 - 08 Apr 2014
Cited by 2 | Viewed by 6151
Abstract
Immune responses directed against clotting factor FVIII (FVIII) seriously complicate treatments for patients with hemophilia A. This response can manifest in congenital hemophilia A patients who generate inhibitor antibodies that bind and inactivate “transplanted” replacement FVIII, as well as in acquired hemophiliacs, whose [...] Read more.
Immune responses directed against clotting factor FVIII (FVIII) seriously complicate treatments for patients with hemophilia A. This response can manifest in congenital hemophilia A patients who generate inhibitor antibodies that bind and inactivate “transplanted” replacement FVIII, as well as in acquired hemophiliacs, whose immune systems have lost tolerance to self-FVIII. Regardless of the mechanism by which production of anti-FVIII inhibitor antibody is triggered, the maintenance of this deleterious response in both congenital and acquired hemophiliacs likely relies upon FVIII specific memory B cells. In this review, the similarities and differences in the kinetics, specificities, and subclasses of antibodies produced in response to allo- and auto-FVIII is outlined. A brief description of the immune cell interactions that contribute to maintenance of antibody response, focusing on development of memory B cells and/or long lived plasma cells is also presented. As current treatments for inhibitor antibodies are not successful in all patients, a better understanding of the functions and persistence of memory B cells specific for FVIII is required. Herein, both clinical and experimental data regarding the effects of immune tolerance induction on memory B cell subpopulations is discussed. Finally, the outcomes of B cell-specific depletion via rituximab in hemophilia and other autoimmune diseases are discussed to highlight insights into the subpopulations of memory B cells that contribute to the development and maintenance of successful tolerance to FVIII. Full article
(This article belongs to the Special Issue B Cells and Immunological Tolerance)
243 KiB  
Review
From Donor to Recipient: Current Questions Relating to Humoral Alloimmunization
by Antoine Prigent, Nicolas Maillard, Léna Absi, Chaker Aloui, Fabrice Cognasse, Sandrine Laradi, Christophe Mariat and Olivier Garraud
Antibodies 2014, 3(1), 130-152; https://doi.org/10.3390/antib3010130 - 20 Feb 2014
Cited by 6 | Viewed by 7071
Abstract
Alloimmunization is an undesirable iatrogenic effect of transfusion and transplantation. In fact, recipients can be considered as responders or not responders, in a continuum from tolerance, including organ transplantation and transfusion, to polyimmunized and refractory patients. New models and large studies have enabled [...] Read more.
Alloimmunization is an undesirable iatrogenic effect of transfusion and transplantation. In fact, recipients can be considered as responders or not responders, in a continuum from tolerance, including organ transplantation and transfusion, to polyimmunized and refractory patients. New models and large studies have enabled a better understanding of the mechanisms that induce specific alloantibody (alloAb) generation. Here, we focus on risk factors of alloimmunization. We review the alloantibody characteristics, summarize the different leukocytes involved in their induction, and suggest some hypotheses. Full article
(This article belongs to the Special Issue B Cells and Immunological Tolerance)
377 KiB  
Review
B Cell Tolerance in Health and Disease
by Murali Gururajan, Vishal J. Sindhava and Subbarao Bondada
Antibodies 2014, 3(1), 116-129; https://doi.org/10.3390/antib3010116 - 19 Feb 2014
Cited by 8 | Viewed by 19790
Abstract
B lymphocyte receptors are generated randomly during the bone marrow developmental phase of B cells. Hence, the B cell repertoire consists of both self and foreign antigen specificities necessitating specific tolerance mechanisms to eliminate self-reactive B cells. This review summarizes the major mechanisms [...] Read more.
B lymphocyte receptors are generated randomly during the bone marrow developmental phase of B cells. Hence, the B cell repertoire consists of both self and foreign antigen specificities necessitating specific tolerance mechanisms to eliminate self-reactive B cells. This review summarizes the major mechanisms of B cell tolerance, which include clonal deletion, anergy and receptor editing. In the bone marrow presentation of antigen in membrane bound form is more effective than soluble form and the role of dendritic cells in this process is discussed. Toll like receptor derived signals affect activation of B cells by certain ligands such as nucleic acids and have been shown to play crucial roles in the development of autoimmunity in several animal models. In the periphery availability of BAFF, a B cell survival factor plays a critical role in the survival of self-reactive B cells. Antibodies against BAFF have been found to be effective therapeutic agents in lupus like autoimmune diseases. Recent developments are targeting anergy to control the growth of chronic lymphocytic leukemia cells. Full article
(This article belongs to the Special Issue B Cells and Immunological Tolerance)
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Graphical abstract

754 KiB  
Review
The PARP1/ARTD1-Mediated Poly-ADP-Ribosylation and DNA Damage Repair in B Cell Diversification
by Jackline J.M. Lasola, Andrea Hodgson, Xin Sun and Fengyi Wan
Antibodies 2014, 3(1), 37-55; https://doi.org/10.3390/antib3010037 - 16 Jan 2014
Cited by 2 | Viewed by 9257
Abstract
ADP-ribosylation is an essential post-translational modification, mediated by a family of proteins named poly-ADP-ribose polymerases/Diphtheria toxin-like ADP-ribosyltransferases (PARPs/ARTDs), that functions to assist in cellular homeostasis through an array of mechanisms. Although the function of PARP1/ARTD1-mediated poly-ADP-ribosylation (PARylation) in response to environmental genotoxic stressors [...] Read more.
ADP-ribosylation is an essential post-translational modification, mediated by a family of proteins named poly-ADP-ribose polymerases/Diphtheria toxin-like ADP-ribosyltransferases (PARPs/ARTDs), that functions to assist in cellular homeostasis through an array of mechanisms. Although the function of PARP1/ARTD1-mediated poly-ADP-ribosylation (PARylation) in response to environmental genotoxic stressors has been extensively studied, its role in the regulation and maintenance of cellular events under times of programmed DNA damage and repair remains to be elucidated. In the case of B cell maturation and differentiation, processes such as V(D)J recombination, somatic hypermutation, and class switch recombination, require the induction of DNA strand breaks for the generation of a varied immunoglobulin repertoire and, thus, serve as a model system to explore the function of PARylation in immunological processes. In this review, we summarize the current understanding of ADP-ribosylation and the PARPs/ARTDs family proteins, in particular PARP1/ARTD1-conferred PARylation, in B cells. Following an overview of PARylation in cellular responses to environmental and spontaneous DNA damage, we discuss the emerging function of PARP1/ARTD1 and PARylation in DNA damage-induced nuclear factor kappaB (NF-κB) signaling and B cell maturation and differentiation. Finally, we conclude by underlining further efforts that are needed to understand how the PARPs/ARTDs family proteins and ADP-ribosylation control the development and function of B cells. Full article
(This article belongs to the Special Issue B Cells and Immunological Tolerance)
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385 KiB  
Review
Regulatory B-Cells in Transplantation
by David San Segundo, Marcos López-Hoyos and Manuel Arias
Antibodies 2013, 2(4), 587-597; https://doi.org/10.3390/antib2040587 - 20 Nov 2013
Cited by 5 | Viewed by 7329
Abstract
B-cells have been long accepted as the main cellular component in humoral responses. Their effector function is based on antibody and cytokine production. The development of donor-specific antibodies by B-cells has deleterious consequences in graft and patients survival. Recently, a new subset of [...] Read more.
B-cells have been long accepted as the main cellular component in humoral responses. Their effector function is based on antibody and cytokine production. The development of donor-specific antibodies by B-cells has deleterious consequences in graft and patients survival. Recently, a new subset of IL-10-secreting B-cells with regulatory capacity in allergic and autoimmune diseases has been shown. Such regulatory function changes the apprehension of B-cells as effector cells and increases the complexity to the immuno-regulatory networks. New therapies targeting B-cells should consider that depleting B-cells potentially impairs regulatory B-cells (Bregs) and that modulating or favoring the maintenance and function of Bregs would be important for the achievement of humoral tolerance. Unfortunately, few direct pieces of evidence of Breg involvement in allograft tolerance models has been described. Here, we summarize the current knowledge of the role of Bregs in transplantation. Full article
(This article belongs to the Special Issue B Cells and Immunological Tolerance)
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353 KiB  
Review
Regulation of Germinal Center Reactions by B and T Cells
by Young Uk Kim, Xindong Liu, Shinya Tanaka, Dat Quoc Tran and Yeonseok Chung
Antibodies 2013, 2(4), 554-586; https://doi.org/10.3390/antib2040554 - 23 Oct 2013
Cited by 3 | Viewed by 16323
Abstract
Break of B cell tolerance to self-antigens results in the development of autoantibodies and, thus, leads to autoimmunity. How B cell tolerance is maintained during active germinal center (GC) reactions is yet to be fully understood. Recent advances revealed several subsets of T [...] Read more.
Break of B cell tolerance to self-antigens results in the development of autoantibodies and, thus, leads to autoimmunity. How B cell tolerance is maintained during active germinal center (GC) reactions is yet to be fully understood. Recent advances revealed several subsets of T cells and B cells that can positively or negatively regulate GC B cell responses in vivo. IL-21-producing CXCR5+ CD4+ T cells comprise a distinct lineage of helper T cells—termed follicular helper T cells (TFH)—that can provide help for the development of GC reactions where somatic hypermutation and affinity maturation take place. Although the function of TFH cells is beneficial in generating high affinity antibodies against infectious agents, aberrant activation of TFH cell or B cell to self-antigens results in autoimmunity. At least three subsets of immune cells have been proposed as regulatory cells that can limit such antibody-mediated autoimmunity, including follicular regulatory T cells (TFR), Qa-1 restricted CD8+ regulatory T cells (CD8+TREG), and regulatory B cells (BREG). In this review, we will discuss our current understanding of GC B cell regulation with specific emphasis on the newly identified immune cell subsets involved in this process. Full article
(This article belongs to the Special Issue B Cells and Immunological Tolerance)
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501 KiB  
Review
Communication between B-Cells and Microbiota for the Maintenance of Intestinal Homeostasis
by Yuying Liu and Jon Marc Rhoads
Antibodies 2013, 2(4), 535-553; https://doi.org/10.3390/antib2040535 - 17 Oct 2013
Cited by 13 | Viewed by 21487
Abstract
The human intestine is populated with an extremely dense and diverse bacterial community. Commensal bacteria act as an important antigenic stimulus producing the maturation of gut-associated lymphoid tissue (GALT). The production of immunoglobulin (Ig) A by B-cells in the GALT is one of [...] Read more.
The human intestine is populated with an extremely dense and diverse bacterial community. Commensal bacteria act as an important antigenic stimulus producing the maturation of gut-associated lymphoid tissue (GALT). The production of immunoglobulin (Ig) A by B-cells in the GALT is one of the immune responses following intestinal colonization of bacteria. The switch of B-cells from IgM to IgA-producing cells in the Peyer’s patches and neighboring lamina propria proceeds by T-cell-dependent and T-cell-independent mechanisms. Several grams of secretory IgA (SIgA) are released into the intestine each day. SIgA serves as a first-line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms. SIgA has a capacity to directly quench bacterial virulence factors, influence the composition of the intestinal microbiota, and promote the transportation of antigens across the intestinal epithelium to GALT and down-regulate proinflammatory responses associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. This review summarizes the reciprocal interactions between intestinal B cells and bacteria, specifically, the formation of IgA in the gut, the role of intestinal IgA in the regulation of bacterial communities and the maintenance of intestinal homeostasis, and the effects of probiotics on IgA levels in the gastrointestinal tract. Full article
(This article belongs to the Special Issue B Cells and Immunological Tolerance)
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