T-bet+ Memory B Cells Link to Local Cross-Reactive IgG upon Human Rhinovirus Infection

Eccles, Jacob D.; Turner, Ronald B.; Kirk, Nicole A.; Muehling, Lyndsey M.; Borish, Larry; Steinke, John W.; Payne, Spencer C.; Wright, Paul; Thacker, Deborah; Lahtinen, Sampo J.; Lehtinen, Markus J.; Heymann, Peter W.; Woodfolk, Judith A.

doi:10.1016/j.celrep.2019.12.027

Cited by 16 publications

(21 citation statements)

References 93 publications

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“…This concept was borne out by our recent work that delineated differential involvement of RV-specific B cells and antibody isotypes according to the anatomic site and time of infection. 69 Thus, the axis linking IFNs secreted in the nose to T H 1 responses in the blood is not necessarily linear. Given that the actions of anti-IgE likely extend beyond the IgE pathway, we speculate that modulation of immune networks both locally and systemically could result in reduced activation, or else rerouting of T H 1 cells.…”

Section: Discussionmentioning

confidence: 99%

Human TH1 and TH2 cells targeting rhinovirus and allergen coordinately promote allergic asthma

Muehling

Heymann

Wright

et al. 2020

Journal of Allergy and Clinical Immunology

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Background: Allergic asthmatic subjects are uniquely susceptible to acute wheezing episodes provoked by rhinovirus. However, the underlying immune mechanisms and interaction between rhinovirus and allergy remain enigmatic, and current paradigms are controversial. Objective: We sought to perform a comprehensive analysis of type 1 and type 2 innate and adaptive responses in allergic asthmatic subjects infected with rhinovirus. Methods: Circulating virus-specific T H 1 cells and allergenspecific T H 2 cells were precisely monitored before and after

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Section: Discussionmentioning

confidence: 99%

Human TH1 and TH2 cells targeting rhinovirus and allergen coordinately promote allergic asthma

Muehling

Heymann

Wright

et al. 2020

Journal of Allergy and Clinical Immunology

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“…[9][10][11][12][13] B cells are constantly circulating through the body's tissues and are also present at the mucosal sites of the respiratory tract, where RV infections mainly take place. 14,15 B cells also represent the major cell population in tonsils 16 where RV can be detected. 17 B cell-mediated humoral immune response plays a central role in controlling RV infections 18,19 with neutralizing serum IgG and secretory IgA in the mucosa detected one to 2 weeks after infection, with a role of protection from re-infection with the same strand.…”

Section: G R a P H I C A L Abstractmentioning

confidence: 99%

Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma

Wirz

Jansen

Satitsuksanoa

et al. 2021

Allergy

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Background Rhinoviruses are the predominant cause of respiratory viral infections and are strongly associated with asthma exacerbations. While humoral immunity plays an important role during virus infections, cellular aspects of this response are less well understood. Here, we investigated the antiviral response of circulating B cells upon experimental rhinovirus infection in healthy individuals and asthma patients. Methods We purified B cells from experimentally infected healthy individuals and patients with asthma and subjected them to total RNA‐sequencing. Rhinovirus‐derived RNA was measured in isolated B cells using a highly sensitive PCR. B cells were stimulated with rhinovirus in vitro to further study gene expression, expression of antiviral proteins and B‐cell differentiation in response rhinovirus stimulation. Protein expression of pro‐inflammatory cytokines in response to rhinovirus was assessed using a proximity extension assay. Results B cells isolated from experimentally infected subjects exhibited an antiviral gene profile linked to IFN‐alpha, carried viral RNA in vivo and were transiently infected by rhinovirus in vitro. B cells rapidly differentiated into plasmablasts upon rhinovirus stimulation. While B cells lacked expression of interferons in response to rhinovirus exposure, co‐stimulation with rhinovirus and IFN‐alpha upregulated pro‐inflammatory cytokine expression suggesting a potential new function of B cells during virus infections. Asthma patients showed extensive upregulation and dysregulation of antiviral gene expression. Conclusion These findings add to the understanding of systemic effects of rhinovirus infections on B‐cell responses in the periphery, show potential dysregulation in patients with asthma and might also have implications during infection with other respiratory viruses.

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“…In a mouse model of SLE, knocking out T-bet specifically in B cells impairs the development of germinal centers, decreases autoantibody levels, and dampens kidney damage and mortality (12). ABCs have been shown to produce proinflammatory cytokines IFNγ and TNFα as well as regulatory cytokine IL-cytomegalovirus (MCMV), gammaherpesvirus68 (gHV68), vaccinia, human immunodeficiency virus (HIV), influenza, hepatitis C, and rhinovirus (15)(16)(17)(18)(19)(20)(21)(22). ABCs have primarily been examined separately in the contexts of viral infection and autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

“…The functional capacities of ABCs and their contribution(s) to MS and EAE are not well understood. ABCs also expand in an array of viral infections including lymphocytic choriomeningitis virus (LCMV), murine cytomegalovirus (MCMV), gammaherpesvirus68 (gHV68), vaccinia, human immunodeficiency virus (HIV), influenza, hepatitis C, and rhinovirus (15)(16)(17)(18)(19)(20)(21)(22). ABCs have primarily been examined separately in the contexts of viral infection and autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

Gammaherpesvirus infection licenses age-associated B cells for pathogenicity in MS and EAE

Mouat

Allanach

Fan

et al. 2021

Preprint

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While age-associated B cells (ABCs) are known to expand and persist following viral infection and during autoimmunity, their interactions are yet to be studied together in these contexts. Epstein-Barr virus (EBV) infection has long been implicated in multiple sclerosis (MS), and it is not known whether ABCs could play a role in mediating viral contribution to autoimmunity. Here, we show that the circulating ABC population is expanded in people with MS and that EBV infection and MS status differentially impact the circulating ABC phenotype. We then directly compared ABCs during viral infection and autoimmunity using mouse models of EBV, gammaherpesvirus 68 (γHV68), and MS, experimental autoimmune encephalomyelitis (EAE). We observed that splenic ABCs are expanded in a sex-biased manner during both latent virus infection and EAE, and each event drives the ABC population to opposing phenotypes. We have previously shown that latent γHV68 infection exacerbates EAE and here we show that mice lacking ABCs fail to display γHV68-enhanced disease. Collectively, these findings indicate that latent viral infection and central nervous system autoimmunity differentially impact the ABC population and suggests that viral infections such as EBV prime ABCs to contribute pathogenically in MS.

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T-bet+ Memory B Cells Link to Local Cross-Reactive IgG upon Human Rhinovirus Infection

Cited by 16 publications

References 93 publications

Human TH1 and TH2 cells targeting rhinovirus and allergen coordinately promote allergic asthma

Human TH1 and TH2 cells targeting rhinovirus and allergen coordinately promote allergic asthma

Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma

Gammaherpesvirus infection licenses age-associated B cells for pathogenicity in MS and EAE

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