Patients with Tuberculosis Have a Dysfunctional Circulating B-Cell Compartment, Which Normalizes following Successful Treatment

Joosten, Simone A.; Meijgaarden, Krista E. van; Nonno, Franca Del; Baiocchini, Andrea; Petrone, Linda; Vanini, Valentina; Smits, Hermelijn H.; Palmieri, Fabrizio; Goletti, Delia; Ottenhoff, Tom H. M.

doi:10.1371/journal.ppat.1005687

Cited by 140 publications

(130 citation statements)

References 42 publications

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“…Although whether these cells respond to self-antigens or are cross-reactive with malarial antigens is not known. Atypical MBCs have been described in several chronic infections including HIV (48, 49) and TB (50) and in autoimmune diseases (51), common features of which are chronic exposure to antigen and inflammation. Clearly inflammation could play a role in driving 9G4 + atypical MBCs in malaria.…”

Section: Discussionmentioning

confidence: 99%

The Regulation of Inherently Autoreactive VH4-34–Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa

Hart

Akkaya

Chida

et al. 2016

The Journal of Immunology

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Plasmodium falciparum malaria is a deadly infectious disease in which antibodies play a critical role in naturally acquired immunity. However, at present the specificity and nature of antibodies elicited in response to malaria is only partially understood. Autoreactivity and polyreactivity are common features of antibody responses in several infections and have been suggested to contribute to effective pathogen-specific antibody responses. Here we report on the regulation of B cells expressing the inherently autoreactive VH4-34 heavy chain (identified by the 9G4 monoclonal antibody) and 9G4+ plasma IgG in adults and children living in a P. falciparum malaria-endemic area in West Africa. The frequency of 9G4+ peripheral blood CD19+ B cells was similar in U.S. adults and African adults and children. However, more 9G4+ B cells appeared in classical and atypical memory B cell compartments in African children and adults as compared to U.S. adults. The levels of 9G4+ IgG increased following acute febrile malaria, but did not increase with age as humoral immunity is acquired or correlate with protection from acute disease. This was the case even though a portion of 9G4+ B cells acquired phenotypes of atypical and classical memory B cells and 9G4+ IgG contained equivalent numbers of somatic hypermutations as compared to all other VHs, a characteristic of secondary antibody repertoire diversification in response to antigen stimulation. Determining the origin and function of 9G4+ B cells and 9G4+ IgG in malaria may contribute to a better understanding of the varied roles of autoreactivity in infectious diseases.

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Section: Discussionmentioning

confidence: 99%

The Regulation of Inherently Autoreactive VH4-34–Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa

Hart

Akkaya

Chida

et al. 2016

The Journal of Immunology

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“…Next to antibody-mediated protection, B-cells also essentially support T-cell responses in TB, but circulating B-cells are dysfunctional and reduced in absolute numbers in patients with active TB (340). The protective effects of Mtb-specific antibodies and B cells in TB suggest that increased BAFF levels may supports host responses by stimulating antibody production and perhaps other B cell functions such as stimulating T cell responses (338).…”

Section: Interactions Between T1-ifns and Th17 Immunity In Tbmentioning

confidence: 99%

Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases

et al. 2017

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The classical paradigm of tuberculosis (TB) immunity, with a central protective role for Th1 responses and IFN-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-γ responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established. These two host responses have been studied in more detail in autoimmune diseases (AID) and show functional interactions that are of potential interest in TB immunity. In this review, we first identify the role of type 1 interferons and Th17 immunity in TB, followed by an overview of interactions between these responses observed in systemic AID. We discuss (i) the effects of GM-CSF-secreting Th17.1 cells and type 1 interferons on CCR2+ monocytes; (ii) convergence of IL-17 and type 1 interferon signaling on stimulating B-cell activating factor production and the central role of neutrophils in this process; and (iii) synergy between IL-17 and type 1 interferons in the generation and function of tertiary lymphoid structures and the associated follicular helper T-cell responses. Evaluation of these autoimmune-related pathways in TB pathogenesis provides a new perspective on recent developments in TB research.

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“…However, interest in the B cell biology of Mtb infections increased with the demonstration that B cells play key roles in the regulation of T cell responses in TB. Joosten et al (58) analyzed the phenotype and function of B cells in individuals with latent TB infection (LTBI) or active TB and in individuals successfully treated for TB. Both individuals with TB and LTBI showed expansion of B cells with an aMBC phenotype, namely CD21 − CD27 − or IgD − CD27 − , and a large portion of the CD21 − CD27 − B cells in some individuals with TB and LTBI expressed FcRL4, CD85, and CD22.…”

Section: Introductionmentioning

confidence: 99%

Atypical memory B cells in human chronic infectious diseases: An interim report

Portugal

Obeng-Adjei

Moir

et al. 2017

Cellular Immunology

165

177

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Immunological memory is a remarkable phenomenon in which survival of an initial infection by a pathogen leads to life-long protection from disease upon subsequent exposure to that same pathogen. For many infectious diseases, long-lived protective humoral immunity is induced after only a single infection in a process that depends on the generation of memory B cells (MBCs) and long-lived plasma cells. However, over the past decade it has become increasingly evident that many chronic human infectious diseases to which immunity is not readily established, including HIV-AIDS, malaria and TB, are associated with fundamental alterations in the composition and functionality of MBC compartments. A common feature of these diseases appears to be a large expansion of what have been termed exhausted B cells, tissue-like memory B cells or atypical memory B cells (aMBCs) that, for simplicity’s sake, we refer to here as aMBCs. It has been suggested that chronic immune activation and inflammation drive the expansion of aMBCs and that in some way aMBCs contribute to deficiencies in the acquisition of immunity in chronic infectious diseases. Although aMBCs are heterogeneous both within individuals and between diseases, they have several features in common including low expression of the cell surface markers that define classical MBCs in humans including CD21 and CD27 and high expression of genes not usually expressed by classical MBCs including T-bet, CD11c and a variety of inhibitory receptors, notably members of the FcRL family. Another distinguishing feature is their greatly diminished ability to be stimulated through their B cell receptors to proliferate, secrete cytokines or produce antibodies. In this review, we describe our current understanding of the phenotypic markers of aMBCs, their specificity in relation to the disease-causing pathogen, their functionality, the drivers of their expansion in chronic infections and their life span. We briefly summarize the features of aMBCs in healthy individuals and in autoimmune disease. We also comment on the possible relationship of human aMBCs and T-bet+, CD11c+ age/autoimmune-associated B cells, also a topic of this review volume.

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Patients with Tuberculosis Have a Dysfunctional Circulating B-Cell Compartment, Which Normalizes following Successful Treatment

Cited by 140 publications

References 42 publications

The Regulation of Inherently Autoreactive VH4-34–Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa

The Regulation of Inherently Autoreactive VH4-34–Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa

Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases

Atypical memory B cells in human chronic infectious diseases: An interim report

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