Protection of mice deficient in mature B cells from West Nile virus infection by passive and active immunization

Giordano, Daniela; Draves, Kevin E.; Young, Lucy B.; Roe, Kelsey; Bryan, Marianne A.; Dresch, C; Richner, Justin M.; Diamond, Michael S.; Gale, Michael; Clark, Edward A.

doi:10.1371/journal.ppat.1006743

Cited by 15 publications

(35 citation statements)

References 74 publications

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“…However, mice deficient in interferon regulatory factor 5 (Irf5 −/− ) infected with WNV exhibited small differences in the type I IFN response also resulted in reduced IgM and IgG secretion that was associated with fewer antigen-specific memory B cells and long-lived plasma cells, which may relate to the reduced proinflammatory cytokine production in these mice [105]. Furthermore, B cell and humoral responses to WNV infection have been suggested to be regulated by many factors related to DCs, the complement system, CD4 + T cells and other immune factors [91,[106][107][108][109][110].…”

Section: Adaptive Humoral Immunitymentioning

confidence: 99%

Current Understanding of West Nile Virus Clinical Manifestations, Immune Responses, Neuroinvasion, and Immunotherapeutic Implications

et al. 2019

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West Nile virus (WNV) is the most common mosquito-borne virus in North America. WNV-associated neuroinvasive disease affects all ages, although elderly and immunocompromised individuals are particularly at risk. WNV neuroinvasive disease has killed over 2300 Americans since WNV entered into the United States in the New York City outbreak of 1999. Despite 20 years of intensive laboratory and clinical research, there are still no approved vaccines or antivirals available for human use. However, rapid progress has been made in both understanding the pathogenesis of WNV and treatment in clinical practices. This review summarizes our current understanding of WNV infection in terms of human clinical manifestations, host immune responses, neuroinvasion, and therapeutic interventions.

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Section: Adaptive Humoral Immunitymentioning

confidence: 99%

Current Understanding of West Nile Virus Clinical Manifestations, Immune Responses, Neuroinvasion, and Immunotherapeutic Implications

et al. 2019

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“…B cells from BAFFR 2/2 mice, which in the absence of BAFF signaling fail to mature beyond the T1 stage, are responsive to Ag-anti-CD180 vaccination, forming Ag-specific plasma cells. This response results in Ag-specific IgG production that is sufficient to protect mice from a lethal viral challenge (4).…”

Section: Discussionmentioning

confidence: 99%

“…Mice deficient for the B cellactivating factor receptor (BAFFR) lack mature B cells but do produce transitional 1 (T1) B cells (3). Vaccination of BAFFR 2/2 mice with West Nile virus (WNV) E protein conjugated to anti-CD180 was sufficient to protect them from a subsequent lethal WNV challenge (4). Remarkably, the addition of an adjuvant was not required to induce protection.…”

mentioning

confidence: 99%

Targeting Antigens to CD180 but Not CD40 Programs Immature and Mature B Cell Subsets to Become Efficient APCs

Roe

Shu

Draves

et al. 2019

The Journal of Immunology

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Targeting Ags to the CD180 receptor activates both B cells and dendritic cells (DCs) to become potent APCs. After inoculating mice with Ag conjugated to an anti-CD180 Ab, B cell receptors were rapidly internalized. Remarkably, all B cell subsets, including even transitional 1 B cells, were programed to process, present Ag, and stimulate Ag-specific CD4 + T cells. Within 24-48 hours, Ag-specific B cells were detectable at T-B borders in the spleen; there, they proliferated in a T cell-dependent manner and induced the maturation of T follicular helper (T FH) cells. Remarkably, immature B cells were sufficient for the maturation of T FH cells after CD180 targeting: T FH cells were induced in BAFFR 2/2 mice (with only transitional 1 B cells) and not in mMT mice (lacking all B cells) following CD180 targeting. Unlike CD180 targeting, CD40 targeting only induced DCs but not B cells to become APCs and thus failed to efficiently induce T FH cell maturation, resulting in slower and lower-affinity IgG Ab responses. CD180 targeting induces a unique program in Ag-specific B cells and to our knowledge, is a novel strategy to induce Ag presentation in both DCs and B cells, especially immature B cells and thus has the potential to produce a broad range of Ab specificities. This study highlights the ability of immature B cells to present Ag to and induce the maturation of cognate T FH cells, providing insights toward vaccination of mature B cell-deficient individuals and implications in treating autoimmune disorders.

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“…B cell and antibody-deficient (μMT) mice and B cell activating factor receptor (BAFFR)-deficient mice are susceptible to infection, but, if treated with immune sera from a wild-type mouse with antibodies to WNV, can be protected from infection (Diamond et al, 2003 ; Giordano et al, 2017 ). Strikingly, the BAFFR-deficient mice can develop sustained protective immunity after treatment with immune sera (Giordano et al, 2017 ). Together, this indicates that passive immunity could be utilized as a therapeutic option for human infection to induce a robust immune response.…”

Section: The Human Immune Response To Wnvmentioning

confidence: 99%

The Immune Responses of the Animal Hosts of West Nile Virus: A Comparison of Insects, Birds, and Mammals

Ahlers

Goodman

2018

Front. Cell. Infect. Microbiol.

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Vector-borne diseases, including arboviruses, pose a serious threat to public health worldwide. Arboviruses of the flavivirus genus, such as Zika virus (ZIKV), dengue virus, yellow fever virus (YFV), and West Nile virus (WNV), are transmitted to humans from insect vectors and can cause serious disease. In 2017, over 2,000 reported cases of WNV virus infection occurred in the United States, with two-thirds of cases classified as neuroinvasive. WNV transmission cycles through two different animal populations: birds and mosquitoes. Mammals, particularly humans and horses, can become infected through mosquito bites and represent dead-end hosts of WNV infection. Because WNV can infect diverse species, research on this arbovirus has investigated the host response in mosquitoes, birds, humans, and horses. With the growing geographical range of the WNV mosquito vector and increased human exposure, improved surveillance and treatment of the infection will enhance public health in areas where WNV is endemic. In this review, we survey the bionomics of mosquito species involved in Nearctic WNV transmission. Subsequently, we describe the known immune response pathways that counter WNV infection in insects, birds, and mammals, as well as the mechanisms known to curb viral infection. Moreover, we discuss the bacterium Wolbachia and its involvement in reducing flavivirus titer in insects. Finally, we highlight the similarities of the known immune pathways and identify potential targets for future studies aimed at improving antiviral therapeutic and vaccination design.

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Protection of mice deficient in mature B cells from West Nile virus infection by passive and active immunization

Cited by 15 publications

References 74 publications

Current Understanding of West Nile Virus Clinical Manifestations, Immune Responses, Neuroinvasion, and Immunotherapeutic Implications

Current Understanding of West Nile Virus Clinical Manifestations, Immune Responses, Neuroinvasion, and Immunotherapeutic Implications

Targeting Antigens to CD180 but Not CD40 Programs Immature and Mature B Cell Subsets to Become Efficient APCs

The Immune Responses of the Animal Hosts of West Nile Virus: A Comparison of Insects, Birds, and Mammals

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