The regulation of gut mucosal IgA B-cell responses: recent developments

Lycke, Nils; Bemark, Mats

doi:10.1038/mi.2017.62

Cited by 157 publications

(125 citation statements)

References 193 publications

(310 reference statements)

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“…A large fraction of IgE is bound to FcεRI, a high-affinity receptor abundant on mast cells and basophils; engagement of IgE by cognate antigen activates FcεRI and promotes degranulation of these cells leading to the rapid release of inflammatory mediators in immediate-type hypersensitivity (Kinet, 1999). IgA and IgM binding to the polymeric Ig receptor on epithelial cells is critical for the delivery of these isotypes to lumenal secretions (Lycke and Bemark, 2017). IgA also exerts effector functions through FcaRI, which is expressed in humans but not in mice (Aleyd et al, 2015).…”

Section: Isotype Switchingmentioning

confidence: 99%

B Cell Responses: Cell Interaction Dynamics and Decisions

Cyster

Allen

2019

Cell

678

634

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B cells and the antibodies they produce have a deeply penetrating influence on human physiology. Here, we review current understanding of how B cell responses are initiated; the different paths to generate short-and long-lived plasma cells, germinal center cells, and memory cells; and how each path impacts antibody diversity, selectivity, and affinity. We discuss how basic research is informing efforts to generate vaccines that induce broadly neutralizing antibodies against viral pathogens, revealing the special features associated with allergen-reactive IgE responses and uncovering the antibody-independent mechanisms by which B cells contribute to health and disease.

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Section: Isotype Switchingmentioning

confidence: 99%

B Cell Responses: Cell Interaction Dynamics and Decisions

Cyster

Allen

2019

Cell

678

634

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“…Generating protective antibody responses in the gut is dependent on affinity matured and long lasting memory B cells in germinal centers of intestinal Peyer's Patches [87]. To this end, DCs, T and B cells in gastrointestinal associated lymphoid tissue (GALT) must be exposed to viral antigens to promote antigen presentation and antibody production ( Figure 1 [88]).…”

Section: Adaptive Immunitymentioning

confidence: 99%

Host Factors Affecting Generation of Immunity Against Porcine Epidemic Diarrhea Virus in Pregnant and Lactating Swine and Passive Protection of Neonates

et al. 2020

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Porcine epidemic diarrhea virus (PEDV) is a highly virulent re-emerging enteric coronavirus that causes acute diarrhea, dehydration, and up to 100% mortality in neonatal suckling piglets. Despite this, a safe and effective PEDV vaccine against highly virulent strains is unavailable, making PEDV prevention and control challenging. Lactogenic immunity induced via the gut-mammary gland-secretory IgA (sIgA) axis, remains the most promising and effective way to protect suckling piglets from PEDV. Therefore, a successful PEDV vaccine must induce protective maternal IgA antibodies that passively transfer into colostrum and milk. Identifying variables that influence lymphocyte migration and IgA secretion during gestation and lactation is imperative for designing maternal immunization strategies that generate the highest amount of lactogenic immune protection against PEDV in suckling piglets. Because pregnancy-associated immune alterations influence viral pathogenesis and adaptive immune responses in many different species, a better understanding of host immune responses to PEDV in pregnant swine may translate into improved maternal immunization strategies against enteric pathogens for multiple species. In this review, we discuss the role of host factors during pregnancy on antiviral immunity and their implications for generating protective lactogenic immunity in suckling neonates.Pathogens 2020, 9, 130 2 of 21 PEDV [2]. The increased rates of protection were associated with high titers of sIgA antibodies in colostrum and milk [2]. This demonstrates that protecting suckling piglets from devastating enteric viral pathogens is dependent on efficient trafficking of intestinal IgA + plasmablasts to the mammary gland (MG) and accumulation of sIgA antibodies in milk, defined as the gut-MG-sIgA axis [2,3]. While it is known that the migration of IgA + plasmablasts to the MG depends on the regulation of mucosal homing receptor and chemokine expression, the mechanisms that regulate this process are much less understood. Identifying variables that influence lymphocyte migration during gestation and lactation is imperative for designing maternal immunization strategies that generate the highest amount of lactogenic immune protection against PEDV in suckling piglets. In this review, we will discuss the role of host factors during pregnancy on antiviral immunity and its implications for generating protective lactogenic immunity against PEDV infection in neonatal suckling piglets. PEDV: A Re-Emerging Enteric CoronavirusPEDV is a highly virulent re-emerging enteric coronavirus belonging to the Alphacoronavirus genus within the family of Coronaviridae. Currently, there are four genera, including Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus, within the Coronaviridae family. Other alphacoronaviruses include transmissible gastroenteritis virus (TGEV) in swine, feline coronaviruses (FCoV), canine coronaviruses (CCoV), ferret enteric coronavirus (FRECV) and two human coronaviruses NL63 and 229E. Additionally, five...

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“…When antigen penetrates through the nasal mucosa, the mucosal immune response is induced by the interaction with APCs in nasal-associated lymphoid tissue (NALT), a representative organized lymphoid tissue of the mucosal immune system, forming a germinal center in the NALT. Clonal expansion of antigen-induced IgA+ B cells is induced to produce antigen-specific IgA [33][34][35]. This procedure may explain the induction of IgA in the groups with intranasal administration, where antigens are exposed to mucous membranes.…”

Section: Discussionmentioning

confidence: 98%

MERS-CoV Spike Protein Vaccine and Inactivated Influenza Vaccine Formulated with Single Strand RNA Adjuvant Induce T-Cell Activation through Intranasal Immunization in Mice

et al. 2020

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The effectiveness of vaccines is enhanced by adding adjuvants. Furthermore, the selection of an inoculation route depends on the type of adjuvant used and is important for achieving optimum vaccine efficacy. We investigated the immunological differences between two types of vaccines-spike protein from the Middle East respiratory syndrome virus and inactivated influenza virus vaccine, in combination with a single-stranded RNA adjuvant-administered through various routes (intramuscular, intradermal, and intranasal) to BALB/c mice. Intramuscular immunization with the RNA adjuvant-formulated spike protein elicited the highest humoral immune response, characterized by IgG1 and neutralizing antibody production. Although intranasal immunization did not elicit a humoral response, it showed extensive T-cell activation through large-scale induction of interferon-γ-and interleukin-2-secreting cells, as well as CD4+ T-cell activation in mouse splenocytes. Moreover, only intranasal immunization induced IgA production. When immunized with the inactivated influenza vaccine, administration of the RNA adjuvant via all routes led to protection after viral challenge, regardless of the presence of a vaccine-specific antibody. Therefore, the inoculation route should depend on the type of immune response needed; i.e., the intramuscular route is suitable for eliciting a humoral immune response, whereas the intranasal route is useful for T-cell activation and IgA induction.

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The regulation of gut mucosal IgA B-cell responses: recent developments

Cited by 157 publications

References 193 publications

B Cell Responses: Cell Interaction Dynamics and Decisions

B Cell Responses: Cell Interaction Dynamics and Decisions

Host Factors Affecting Generation of Immunity Against Porcine Epidemic Diarrhea Virus in Pregnant and Lactating Swine and Passive Protection of Neonates

MERS-CoV Spike Protein Vaccine and Inactivated Influenza Vaccine Formulated with Single Strand RNA Adjuvant Induce T-Cell Activation through Intranasal Immunization in Mice

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