Immune Mediators of Rotavirus Antigenemia Clearance in Mice

Marcelin, Glendie; Miller, Amber; Blutt, Sarah E.; Conner, Margaret E.

doi:10.1128/jvi.00844-10

Cited by 9 publications

(12 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3B and Table 1), strongly suggesting a role for circulating IgM ϩ mBc in the provision of systemic RV immunity. Consistent with our results, it was recently shown that in mice, murine lymphocytes are necessary to clear antigenemia but that neither T nor B cells are absolutely required for this effect (44).…”

Section: Discussionsupporting

confidence: 81%

“…Human circulating IgM ϩ mBc are enriched in nonneutralizing anti-VP6 rather than neutralizing anti-VP4 or VP7-expressing cells (51,64), and the anti-VP6 antibodies from these IgM ϩ mBc are probably responsible for the decrease in circulating RV antigen. In support of this prediction, the transfer of both neutralizing and nonneutralizing antibodies to chronically infected immunodeficient mice delayed the onset and duration of antigenemia (44). Over 90% of acutely infected children have circulating RV antigen in their plasma, which disappears during the convalescence phase (7).…”

Section: Discussionmentioning

confidence: 67%

See 1 more Smart Citation

Human Rotavirus-Specific IgM Memory B Cells Have Differential Cloning Efficiencies and Switch Capacities and Play a Role in Antiviral ImmunityIn Vivo

Narváez

Feng

Vásquez

et al. 2012

J Virol

View full text Add to dashboard Cite

Protective immunity to rotavirus (RV) is primarily mediated by antibodies produced by RV-specific memory B cells (RV-mBc).Of note, most of these cells express IgM, but the function of this subset is poorly understood. Here, using limiting dilution assays of highly sort-purified human IgM ؉ mBc, we found that 62% and 21% of total (non-antigen-specific) IgM ؉ and RV-IgM ؉ mBc, respectively, switched in vitro to IgG production after polyclonal stimulation. Moreover, in these assays, the median cloning efficiencies of total IgM ؉ (17%) and RV-IgM ؉ (7%) mBc were lower than those of the corresponding switched (IgG ؉ IgA ؉ ) total (34%) and RV-mBc (17%), leading to an underestimate of their actual frequency. In order to evaluate the in vivo role of IgM ؉ RV-mBc in antiviral immunity, NOD/Shi-scid interleukin-2 receptor-deficient (IL-2R␥null ) immunodeficient mice were adoptively transferred highly purified human IgM ؉ mBc and infected with virulent murine rotavirus. These mice developed high titers of serum human RV-IgM and IgG and had significantly lower levels than control mice of both antigenemia and viremia. Finally, we determined that human RV-IgM ؉ mBc are phenotypically diverse and significantly enriched in the IgM hi IgD low subset. Thus, RV-IgM ؉ mBc are heterogeneous, occur more frequently than estimated by traditional limiting dilution analysis, have the capacity to switch Ig class in vitro as well as in vivo, and can mediate systemic antiviral immunity.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 67%

Human Rotavirus-Specific IgM Memory B Cells Have Differential Cloning Efficiencies and Switch Capacities and Play a Role in Antiviral ImmunityIn Vivo

Narváez

Feng

Vásquez

et al. 2012

J Virol

View full text Add to dashboard Cite

show abstract

“…This is supported by studies in mice that lack expression of the TNF family member LTα that do not develop Peyer’s patches (203) and these mice are unable to clear rotavirus infection or produce stool rotavirus-specific IgA following virus exposure (204). This is similar to the response seen in B cell, IgA, and J-chain knockout animals (140, 179, 194, 197). Therefore, Peyer’s patch B cells appear to be critical for intestinal rotavirus-specific IgA.…”

Section: Iga and Rotavirussupporting

confidence: 80%

“…Mice lacking B cells exhibit significant delays in clearance of a rotavirus infection (194) and fail to establish protective immunity against a second infection (140). These deficits contrast to the limited to no defects in clearance or protection in mice lacking T cells (118, 195).…”

Section: Iga and Rotavirusmentioning

confidence: 99%

The Gastrointestinal Frontier: IgA and Viruses

Blutt

Conner

2013

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Viral gastroenteritis is one of the leading causes of diseases that kill ~2.2 million people worldwide each year. IgA is one of the major immune effector products present in the gastrointestinal tract yet its importance in protection against gastrointestinal viral infections has been difficult to prove. In part this has been due to a lack of small and large animal models in which pathogenesis of and immunity to gastrointestinal viral infections is similar to that in humans. Much of what we have learned about the role of IgA in the intestinal immune response has been obtained from experimental animal models of rotavirus infection. Rotavirus-specific intestinal IgA appears to be one of the principle effectors of long term protection against rotavirus infection. Thus, there has been a focus on understanding the immunological pathways through which this virus-specific IgA is induced during infection. In addition, the experimental animal models of rotavirus infection provide excellent systems in which new areas of research on viral-specific intestinal IgA including the long term maintenance of viral-specific IgA.

show abstract

“…B cells represent an important component of the protective immune response against RV: mice deficient in B cells are susceptible to reinfection as adults (23), and antibodies, but not T cells, mediate long-term protection from reinfection (24)(25)(26)(27). Additionally, RV-specific serum antibodies are sufficient to suppress RV antigenemia in the absence of T cells (28), and transfer of B cells is sufficient to effect RV clearance in chronically infected Rag-knockout mice (29). Passive transfer of highly purified human IgM memory B cells into NOD/Shi-SCID IL-2Rγ null immunodeficient mice suppresses systemic RV viremia, but not fecal shedding (30).…”

Section: Introductionmentioning

confidence: 99%

Plasmacytoid dendritic cells promote rotavirus-induced human and murine B cell responses

Deal

Lahl²,

Narváez³

et al. 2013

J. Clin. Invest.

View full text Add to dashboard Cite

B cell-dependent immunity to rotavirus, an important intestinal pathogen, plays a significant role in viral clearance and protects against reinfection. Human in vitro and murine in vivo models of rotavirus infection were used to delineate the role of primary plasmacytoid DCs (pDCs) in initiating B cell responses. Human pDCs were necessary and sufficient for B cell activation induced by rotavirus. Type I IFN recognition by B cells was essential for rotavirus-mediated B cell activation in vitro and murine pDCs and IFN-α/β-mediated B cell activation after in vivo intestinal rotavirus infection. Furthermore, rotavirus-specific serum and mucosal antibody responses were defective in mice lacking functional pDCs at the time of infection. These data demonstrate that optimal B cell activation and virus-specific antibody secretion following mucosal infection were a direct result of pDC-derived type I IFN. Importantly, viral shedding significantly increased in pDC-deficient mice, suggesting that pDC-dependent antibody production influences viral clearance. Thus, mucosal pDCs critically influence the course of rotavirus infection through rotavirus recognition and subsequent IFN production and display powerful adjuvant properties to initiate and enhance humoral immunity.

show abstract

Immune Mediators of Rotavirus Antigenemia Clearance in Mice

Cited by 9 publications

References 67 publications

Human Rotavirus-Specific IgM Memory B Cells Have Differential Cloning Efficiencies and Switch Capacities and Play a Role in Antiviral ImmunityIn Vivo

Human Rotavirus-Specific IgM Memory B Cells Have Differential Cloning Efficiencies and Switch Capacities and Play a Role in Antiviral ImmunityIn Vivo

The Gastrointestinal Frontier: IgA and Viruses

Plasmacytoid dendritic cells promote rotavirus-induced human and murine B cell responses

Contact Info

Product

Resources

About