Glycolipid‐activated NKT cells support the induction of persistent plasma cell responses and antibody titers

Devera, T. Scott; Shah, Hemangi B.; Lang, Gillian A.; Lang, Mark L.

doi:10.1002/eji.200738000

Cited by 47 publications

(87 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immulon 4 enzyme-linked immunosorbent assay (ELISA) plates (Dynex, Chantilly, VA) were coated with CTD1 or CTD2, and specific endpoint IgG1, IgG2b, IgG2c, and IgG3 titers were determined as described previously (39). In adoptive transfers, IgH b was also detected by ELISA as described previously (37).…”

Section: Methodsmentioning

confidence: 99%

Memory B Cells Encode Neutralizing Antibody Specific for Toxin B from the Clostridium difficile Strains VPI 10463 and NAP1/BI/027 but with Superior Neutralization of VPI 10463 Toxin B

et al. 2016

View full text Add to dashboard Cite

T he role of immune cell memory in Clostridium difficile infection (CDI) remains poorly understood. CDI is complicated by a high frequency of recurrence, often after disease has apparently resolved, and can be associated with progressively worsening pathology and ultimately death (1). However, patients that develop antibodies (Ab) capable of neutralizing two toxins secreted by C. difficile (TcdA and TcdB) are less likely to experience recurrence (reviewed in reference 2). This suggests that memory B (Bmem) cells may contribute to resistance to reinfection by encoding toxin-neutralizing Ab. Bmem cells have typically undergone affinity maturation and Ab class switch in the germinal centers of secondary lymphoid organs (3). Bmem cells are therefore poised to respond rapidly to booster vaccinations or infection, by rapidly differentiating into plasma cells that secrete class-switched, highaffinity Ab (4). Such plasma cells may display a range of short-toextreme longevity, be associated with transient or sustained Ab titers, or secrete neutralizing or nonneutralizing Ab (5-7).In earlier studies, a correlation between bacterial load and advanced age was observed during CDI, with older individuals lacking toxin-neutralizing Ab (8). In more recent work, the probability of HIV-positive patients experiencing CDI increased as their CD4 ϩ T-cell counts declined (9), which could be partly attributable to altered CD4 ϩ T-cell-dependent B cell function (10). Indeed, there is growing concern about CDI in a variety of immunocompromised individuals, including organ transplant recipients (reviewed in reference 11). These observations highlight the wellrecognized importance of B cell responses and production of toxin-neutralizing antibodies in resisting CDI. However, the underlying characteristics of the Bmem cellular response and their contributions to production of toxin-neutralizing Ab have not been described.CDI is best known as a disease of the gastrointestinal tract, causing diarrhea, and this infection may progress to a severe pathological condition in which pseudomembranous colitis and toxic megacolon are evident (1, 2). However, CDI-associated mortality may be attributable to systemic sequelae of the disease (12). Although large-scale epidemiological studies are lacking, reported systemic complications include hepatic abscesses (13), ascites (14), pleural effusion with acute respiratory distress (15, 16), and severe sepsis and multiorgan dysfunction (17).TcdA and TcdB are large clostridial toxins that contribute sub-

show abstract

Section: Methodsmentioning

confidence: 99%

Memory B Cells Encode Neutralizing Antibody Specific for Toxin B from the Clostridium difficile Strains VPI 10463 and NAP1/BI/027 but with Superior Neutralization of VPI 10463 Toxin B

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Coadministration of a-GC with immunizing antigen to mice results in enhanced production of antibodies specific for the antigen [170][171][172], demonstrating that the adjuvant effect of iNKT cells is antigen-specific. This help provided by iNKT cells results in the induction of long-lived antibody-secreting plasma cells, affinity maturation and the generation of memory B cells [172][173][174][175]. iNKT cells can also provide help for B cells specific for lipid-containing antigens internalized through the B cell receptor [176,177].…”

mentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

View full text Add to dashboard Cite

a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

show abstract

“…However, unlike other classic adjuvants, αGalCer was shown to enhance Ab production against both TD and TI Ags also in mice lacking CD4 + Th cells [34,35], suggesting the possible provision of CD1-dependent B-cell help by iNKT cells in vivo. Immunization of mice lacking iNKT cells revealed that iNKT cells also display a spontaneous (non-αGalCer induced) role in inducing and/or maintaining the circulating Ab levels through the control of plasma cell homeostasis [34,36], which was found to depend on the iNKT-cell expression of B-cell activating factor and a proliferation-inducing ligand (APRIL) [37]. …”

mentioning

confidence: 99%

iNKT‐cell help to B cells: A cooperative job between innate and adaptive immune responses

2014

View full text Add to dashboard Cite

T-cell help to B lymphocytes is one of the most important events in adaptive immune responses in health and disease. It is generally delivered by cognate CD4 + T follicular helper (T FH ) cells via both cell-to-cell contacts and soluble mediators, and it is essential for both the clonal expansion of antibody (Ab)-secreting B cells and memory B-cell formation. CD1d-restricted invariant natural killer T (iNKT) cells are a subset of innate-like T lymphocytes that rapidly respond to stimulation with specific lipid antigens (Ags) that are derived from infectious pathogens or stressed host cells. Activated iNKT cells produce a wide range of cytokines and upregulate costimulatory molecules that can promote activation of dendritic cells (DCs), natural killer (NK) cells, and T cells. A decade ago, we discovered that iNKT cells can help B cells to proliferate and to produce IgG Abs in vitro and in vivo. This adjuvant-like function of Ag-activated iNKT cells provides a flexible set of helper mechanisms that expand the current paradigm of T-cell-B-cell interaction and highlights the potential of iNKT-cell targeting vaccine formulations.Keywords: B-cell help r CD1d r T follicular helper cells r vaccines IntroductionThe production of neutralizing antibodies (Abs) by B cells represents a major parameter of host defense against infectious pathogens and is a key component of protective immune responses elicited by vaccines [1]. The innate and adaptive arms of the immune system are functionally separated, but seem to be highly coordinated to ensure an optimal outcome of immune responses. Although innate and adaptive immune cells are endowed with very distinct functions and timing of response, there are specialized lymphocyte subsets that straddle the two programs, and these cells have been defined as innate-like lymphocytes [2]. CD1d-rectricted invariant Vα14 natural killer T (iNKT) cells are one of the best characterized types of innate-like T lymphocytes, which display multiple effector functions upon activation [3]. Here, we review the mechanisms through which iNKT cells help B cells to promote Ab production and memory formation.Correspondence: Dr. Paolo Dellabona e-mail: dellabona.paolo@hsr.itThe TD and TI paradigm of the B-cell response B-cell responses are generally described as T-dependent (TD) or T-independent (TI), based on the requirement for T-cell help for Ab production. TD responses are induced by protein antigens (Ags) that are recognized by specific B cells in the presence of cognate T-cell help, which is provided by a specialized subset of CD4 + T helper (Th) cells called T follicular helper (T FH ) cells [4]. Ags reach the follicles, the B-cell zone of secondary lymphoid organs, and activate B cells upon binding to the specific B-cell receptors (BCRs [5]). This leads to Ag internalization, presentation of the processed Ag peptides into MHC class II (MHC II) molecules, and migration of the activated B cells to the border of the T-B-cell zone [4]. T FH cells are induced in the T-cell zone by dendritic cells (DCs) t...

show abstract

Glycolipid‐activated NKT cells support the induction of persistent plasma cell responses and antibody titers

Cited by 47 publications

References 43 publications

Memory B Cells Encode Neutralizing Antibody Specific for Toxin B from the Clostridium difficile Strains VPI 10463 and NAP1/BI/027 but with Superior Neutralization of VPI 10463 Toxin B

Memory B Cells Encode Neutralizing Antibody Specific for Toxin B from the Clostridium difficile Strains VPI 10463 and NAP1/BI/027 but with Superior Neutralization of VPI 10463 Toxin B

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

iNKT‐cell help to B cells: A cooperative job between innate and adaptive immune responses

Contact Info

Product

Resources

About