Human B cells have an active phagocytic capability and undergo immune activation upon phagocytosis of Mycobacterium tuberculosis

Zhu, Qi; Zhang, Min; Shi, Ming; Liu, Yang; Zhao, Qing; Wang, Wenjing; Zhang, Guangyun; Yang, Long-Xiu; Jin, Zhi; Zhang, Lin; Hu, Gengyao; Chen, Pin; Yang, Yining; Dai, Wen; Liu, Tingting; He, Ying; Feng, Guodong; Zhao, Gang

doi:10.1016/j.imbio.2015.12.003

Cited by 64 publications

(41 citation statements)

References 48 publications

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“…This process is well documented for myeloid cells . B‐cells are infected by M. tuberculosis through a process of micropinocytosis and express death receptors. The manner in which a general loss of T‐cells occur during tuberculosis is not well defined .…”

Section: Discussionmentioning

confidence: 93%

B‐cells with a FasL expressing regulatory phenotype are induced following successful anti‐tuberculosis treatment

Rensburg

Kleynhans

Keyser

et al. 2016

Immunity Inflam & Disease

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IntroductionStudies show that B‐cells, in addition to producing antibodies and antigen‐presentation, are able to produce cytokines as well. These include regulatory cytokines such as IL‐10 by regulatory B‐cells. Furthermore, a rare regulatory subset of B‐cells have the potential to express FasL, which is a death‐inducing ligand. This subset of B‐cells have a positive role during autoimmune disease, but has not yet been studied during tuberculosis. These FasL‐expressing B‐cells are induced by bacterial LPS and CpG, thus we hypothesized that this phenotype might be induced during tuberculosis as well.MethodsB‐cells from participants with TB (at diagnosis and during treatment) and controls were collected, and analyzed by means of real‐time PCR and flow cytometry. In addition to this, BAL was collected from TB participants as well and analyzed by means of MAGPix (multi‐cytokine) technology.ResultsGene expression analysis show that FASL transcript levels increase by the end of treatment. Similarly, phenotypic analysis show that there is a higher frequency of FasL‐expressing B‐cells by the end of treatment.ConclusionCollectively, these results indicate that these FasL‐expressing B‐cells are being induced during anti‐TB treatment, and thus may play a positive role. Further studies are required to elucidate this.

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Section: Discussionmentioning

confidence: 93%

B‐cells with a FasL expressing regulatory phenotype are induced following successful anti‐tuberculosis treatment

Rensburg

Kleynhans

Keyser

et al. 2016

Immunity Inflam & Disease

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“…CD8 + T cells have an essential but underappreciated role in the control of TB (12) and are critical for both natural and vaccine-induced immunity in nonhuman primates (NHPs) (13,14). In contrast, the role of B cells in immunity to TB is less well understood, although it appears they are required for the development of optimal immune responses to Mtb via various regulatory mechanisms (15)(16)(17).…”

Section: Nonhuman Primate | B Cells | Tuberculosis | Cd4 T Cells | CDmentioning

confidence: 99%

CD4 ⁺ T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection

Foreman

Mehra

LoBato

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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202

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The synergy between Mycobacterium tuberculosis (Mtb) and HIV in coinfected patients has profoundly impacted global mortality because of tuberculosis (TB) and AIDS. HIV significantly increases rates of reactivation of latent TB infection (LTBI) to active disease, with the decline in CD4 + T cells believed to be the major causality. In this study, nonhuman primates were coinfected with Mtb and simian immunodeficiency virus (SIV), recapitulating human coinfection. A majority of animals exhibited rapid reactivation of Mtb replication, progressing to disseminated TB and increased SIV-associated pathology. Although a severe loss of pulmonary CD4 + T cells was observed in all coinfected macaques, a subpopulation of the animals was still able to prevent reactivation and maintain LTBI. Investigation of pulmonary immune responses and pathology in this cohort demonstrated that increased CD8 + memory T-cell proliferation, higher granzyme B production, and expanded B-cell follicles correlated with protection from reactivation. Our findings reveal mechanisms that control SIV-and TB-associated pathology. These CD4-independent protective immune responses warrant further studies in HIV coinfected humans able to control their TB infection. Moreover, these findings will provide insight into natural immunity to Mtb and will guide development of novel vaccine strategies and immunotherapies.Nonhuman primate | B cells | tuberculosis | CD4 T cells | CD8 T cells

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“…Phagocytosis is generally believed to be carried out by specialized APCs [10], but not by naïve B cells [11,12]. Notwithstanding, it has been described that a specific subpopulation of B cells, B1 B cells, is also able to phagocytose particles including bacteria [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Antigen phagocytosis by B cells is required for a potent humoral response

et al. 2018

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Successful vaccines rely on activating a functional humoral response that results from promoting a proper germinal center (GC) reaction. Key in this process is the activation of follicular B cells that need to acquire antigens and to present them to cognate CD4 T cells. Here, we report that follicular B cells can phagocytose large antigen‐coated particles, a process thought to be exclusive of specialized antigen‐presenting cells such as macrophages and dendritic cells. We show that antigen phagocytosis by B cells is BCR‐driven and mechanistically dependent on the GTPase RhoG. Using Rhog −/− mice, we show that phagocytosis of antigen by B cells is important for the development of a strong GC response and the generation of high‐affinity class‐switched antibodies. Importantly, we show that the potentiation effect of alum, a common vaccine adjuvant, requires direct phagocytosis of alum–antigen complexes by B cells. These data suggest a new avenue for vaccination approaches by aiming to deliver 1–3 μm size antigen particles to follicular B cells.

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Human B cells have an active phagocytic capability and undergo immune activation upon phagocytosis of Mycobacterium tuberculosis

Cited by 64 publications

References 48 publications

B‐cells with a FasL expressing regulatory phenotype are induced following successful anti‐tuberculosis treatment

B‐cells with a FasL expressing regulatory phenotype are induced following successful anti‐tuberculosis treatment

CD4 ⁺ T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection

Antigen phagocytosis by B cells is required for a potent humoral response

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Human B cells have an active phagocytic capability and undergo immune activation upon phagocytosis of Mycobacterium tuberculosis

Cited by 64 publications

References 48 publications

B‐cells with a FasL expressing regulatory phenotype are induced following successful anti‐tuberculosis treatment

B‐cells with a FasL expressing regulatory phenotype are induced following successful anti‐tuberculosis treatment

CD4 + T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection

Antigen phagocytosis by B cells is required for a potent humoral response

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CD4 ⁺ T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection