Non‐neutralizing antibodies protect from chronic LCMV infection independently of activating FcγR or complement

Richter, Kirsten; Oxenius, Annette

doi:10.1002/eji.201343566

Cited by 33 publications

(45 citation statements)

References 48 publications

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“…A similar effect on viral replication in tissues was also observed (Fig 1C). Development of neutralizing antibody titers are delayed after cl13 infection, non-neutralizing antibodies may be important(9, 13, 14) (data not shown) defective FcR function impairs viral control during cl13 infection(15, 16). Thus, non-neutralizing functions of T-bet dependent antibody or B cell responses may play a role in chronic LCMV infection.…”

Section: Resultsmentioning

confidence: 98%

Cutting Edge: B Cell–Intrinsic T-bet Expression Is Required To Control Chronic Viral Infection

Barnett

Staupe

Odorizzi

et al. 2016

The Journal of Immunology

155

177

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The role of antibody and B cells in preventing infection is established. In contrast, the role of B cell responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in humans) can prevent acute infections and T-bet promotes IgG2a isotype switching. However, whether IgG2a and B cell-expressed T-bet influence the host-pathogen balance during persisting infections is unclear. Here we demonstrate that B cell specific loss of T-bet prevents control of persisting viral infection. T-bet in B cells not only controlled IgG2a production, but also mucosal localization, proliferation, glycosylation, and a broad transcriptional program. T-bet controlled a broad antiviral program in addition to IgG2a since T-bet in B cells was important even in the presence of virus-specific IgG2a. Our data supports a model in which T-bet is a universal controller of antiviral immunity across multiple immune lineages.

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Section: Resultsmentioning

confidence: 98%

Cutting Edge: B Cell–Intrinsic T-bet Expression Is Required To Control Chronic Viral Infection

Barnett

Staupe

Odorizzi

et al. 2016

The Journal of Immunology

155

177

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“…CD4 + T cells and antibody production by B cells are crucial for resolving chronic viral infections (Bergthaler et al, 2009; Planz et al, 1997; Richter and Oxenius, 2013). There is an increase in CD8 + T cell exhaustion and delayed virus clearance when CD4 + T cells are depleted during chronic LCMV infection (Matloubian et al, 1994).…”

Section: Resultsmentioning

confidence: 99%

T Follicular Helper Cell-Dependent Clearance of a Persistent Virus Infection Requires T Cell Expression of the Histone Demethylase UTX

et al. 2015

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Summary Epigenetic changes, including histone methylation, control T cell differentiation and memory formation, though the enzymes that mediate these processes are not clear. We show that UTX, a histone H3 lysine 27 (H3K27) demethylase, supports T follicular helper (Tfh) cell responses that are essential for B cell antibody generation and the resolution of chronic viral infections. Mice with a T cell-specific UTX deletion had fewer Tfh cells, reduced germinal center responses, lacked virus-specific IgG, and were unable to resolve chronic lymphocytic choriomeningitis virus infections. UTX-deficient T cells showed decreased expression of interleukin-6 receptor-α and other Tfh cell-related genes that were associated with increased H3K27 methylation. Additionally, Turner Syndrome subjects, who are predisposed to chronic ear infections, had reduced UTX expression in immune cells and decreased circulating CD4+ CXCR5+ T cell frequency. Thus, we identify a critical link between UTX in T cells and immunity to infection.

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“…The data in Figure 7 show that B cell-depletion impairs immunity to disseminating virus infection, implying that B cells directly or indirectly contribute factors that prevent T cell exhaustion. B cell production of cytokines or antibody may contribute to the resolution of infection (76, 94, 95). Overall, our findings suggest that B cell-depletion therapies in people will increase their susceptibility to opportunistic infections.…”

Section: Discussionmentioning

confidence: 99%

B Cell Depletion Curtails CD4+ T Cell Memory and Reduces Protection against Disseminating Virus Infection

Misumi

Whitmire

2014

The Journal of Immunology

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Dynamic interactions between CD4+ T cells and B cells are needed for humoral immunity and CD4+ T cell memory. It is not known whether B cells are needed early on to induce the formation of memory precursor cells or are needed later to sustain memory cells. Herein, primary and memory CD4+ T cells responses were followed in wildtype mice that were depleted of mature B cells by anti-CD20 before or different times after acute lymphocytic choriomeningitis virus (LCMV) infection. The antibody treatment led to a 1000-fold reduction in B cell number that lasted 6 weeks. Primary virus-specific CD4+ Th1 cells were generated in B cell-depleted mice, however, there was a decrease in the CD4+Ly6CloTbet+ memory precursor population and a corresponding 4-fold reduction in CD4+ memory cell number. Memory T cells showed impaired cytokine production when they formed without B cells. B cell-depletion had no effect on established memory populations. During disseminating virus infection, B cell depletion led to sustained weight loss, functional exhaustion of CD4+ and CD8+ T cells, and prevented mice from resolving the infection. Thus, B cells contribute to the establishment and survival of memory CD4+ T cells following acute infection and play an essential role in immune protection against disseminating virus infection.

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Non‐neutralizing antibodies protect from chronic LCMV infection independently of activating FcγR or complement

Abstract: Chronic viral infections lead to CD8

Cited by 33 publications

References 48 publications

Cutting Edge: B Cell–Intrinsic T-bet Expression Is Required To Control Chronic Viral Infection

Cutting Edge: B Cell–Intrinsic T-bet Expression Is Required To Control Chronic Viral Infection

T Follicular Helper Cell-Dependent Clearance of a Persistent Virus Infection Requires T Cell Expression of the Histone Demethylase UTX

B Cell Depletion Curtails CD4+ T Cell Memory and Reduces Protection against Disseminating Virus Infection

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