scholarly journals The Wanderings of Gut-Derived IgA Plasma Cells: Impact on Systemic Immune Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Selina J. Keppler ◽  
Marie Christine Goess ◽  
Julia M. Heinze
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
B Cell ◽  
Protective Immunity ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Commensal Microbiota ◽  
Mucosal Tissues ◽  
Iga Antibodies ◽  
Antibody Secreting Cells

Humoral immunity is mainly mediated by a B cell population highly specialized to synthesize and secrete large quantities of antibodies – the antibody-secreting cells (ASC). In the gastrointestinal environment, a mixture of foreign antigens from the diet, commensal microbiota as well as occasional harmful pathogens lead to a constant differentiation of B cells into ASC. Due to this permanent immune response, more than 80% of mammalian ASC reside in the gut, of which most express immunoglobulin A (IgA). IgA antibodies contribute to intestinal homeostasis and can mediate protective immunity. Recent evidence points at a role for gut-derived ASC in modulating immune responses also outside of mucosal tissues. We here summarize recent evidence for wandering ASC, their antibodies and their involvement in systemic immune responses.

scholarly journals The essential role played by B cells in supporting protective immunity againstTrichuris murisinfection is dependent on host genetic background and is independent of antibody

2019 ◽  
Author(s):  
Rinal Sahputra ◽  
Dominik Ruckerl ◽  
Kevin Couper ◽  
Werner Muller ◽  
Kathryn J Else
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Genetic Background ◽  
Protective Immunity ◽  
Essential Role ◽  
Accessory Cells ◽  
Ifn Γ ◽  
Anti Cd20

AbstractThis study investigates the role of B cells in immunity toTrichuris muris(T. muris) infection in two genetically distinct strains of mouse, using anti-CD20 monoclonal antibody (mAb) (Genentech-clone 5D2) to deplete B cells. Data is presented for the mouse strains: C57BL/6 and BALB/c, which mount mixed Th1/Th2, and highly polarised Th2 immune responses toT. muris, respectively. C57BL/6 mice receiving anti-CD20 treatment prior to and during, or anti-CD20 treatment that commenced two weeks post infection (p.i.), were susceptible toT. muris. Parasite-specific IgG1 antibodies were absent and Th2 type cytokines produced by mesenteric lymph nodes cells from mice receiving α-CD20 mAb treatment were significantly lower than produced by cells from isotype control treated mice. T follicular helper cells were also significantly reduced. Importantly, and in complete contrast, BALB/c mice were still able to expelT.murisin the absence of B cells, revealing that the essential role played by B cells in protective immunity was dependent on genetic background. To explore whether the important role played by the B cell in the protective immune response of C57BL/6 mice was in enabling strong Th2 responses in the presence of IFN-γ, IFN-γ was blocked using anti-IFN-γ mAb post B cell depletion. Depleting IFN-γ, in the absence of B cells restored worm expulsion in the absence of parasite-specific IgG1/IgG2c and partially rescued theT. murisspecific IL-13 response. Thus, our data suggest an important, antibody independent role for B cells in supporting Th2 type immune responses in mixed IFN-γ-rich Th1/Th2 immune response settings.Author summaryHow B cells contribute to protective immunity against parasitic nematodes remains unclear, with their importance as accessory cells under-explored. This study reveals that, on some genetic backgrounds, B cells are important for the expulsion ofT. murisby acting as accessory cells, supporting Th2 immune responses.

Blood-borne human plasma cells in steady state are derived from mucosal immune responses

Blood ◽  
2009 ◽  
Vol 113 (11) ◽  
pp. 2461-2469 ◽  
Author(s):  
Henrik E. Mei ◽  
Taketoshi Yoshida ◽  
Wondossen Sime ◽  
Falk Hiepe ◽  
Kathi Thiele ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Immune Responses ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Low Frequency ◽  
Substantial Contribution ◽  
Immune Reactions ◽  
Humoral Immune ◽  
Humoral Immune Responses

AbstractProviding humoral immunity, antibody-secreting plasma cells and their immediate precursors, the plasmablasts, are generated in systemic and mucosal immune reactions. Despite their key role in maintaining immunity and immunopathology, little is known about their homeostasis. Here we show that plasmablasts and plasma cells are always detectable in human blood at low frequency in any unimmunized donor. In this steady state, 80% of plasmablasts and plasma cells express immunoglobulin A (IgA). Expression of a functional mucosal chemokine receptor, C-C motif receptor 10 (CCR10) and the adhesion molecule β7 integrin suggests that these cells come from mucosal immune reactions and can return to mucosal tissue. These blood-borne, CCR10+ plasmablasts also are attracted by CXCL12. Approximately 40% of plasma cells in human bone marrow are IgA+, nonmigratory, and express β7 integrin and CCR10, suggesting a substantial contribution of mucosal plasma cells to bone marrow resident, long-lived plasma cells. Six to 8 days after parenteral tetanus/diphtheria vaccination, intracellular IgG+ cells appear in blood, both CD62L+, β7 integrin−, dividing, vaccine-specific, migratory plasmablasts and nondividing, nonmigratory, CD62L− plasma cells of different specificities. Systemic vaccination does not impact on peripheral IgA+ plasmablast numbers, indicating that mucosal and systemic humoral immune responses are regulated independent of each other.

The immune response and the evaluation of acquired immunity against gastrointestinal nematodes in cattle: a review

Parasitology ◽  
2000 ◽  
Vol 120 (7) ◽  
pp. 25-42 ◽  
Author(s):  
E. CLAEREBOUT ◽  
J. VERCRUYSSE
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Protective Immunity ◽  
Current Knowledge ◽  
Small Ruminants ◽  
Gastrointestinal Nematodes ◽  
Gastrointestinal Parasites ◽  
Acquired Immunity ◽  
Immunological Parameters ◽  
Iga Response

The present review discusses the immune responses to gastrointestinal nematodes in cattle and the different immunological and parasitological parameters used to assess acquired immunity. Measuring acquired immunity to gastrointestinal nematodes in cattle (e.g. for the evaluation of candidate parasite vaccines) is hampered by the limited understanding of bovine immune responses against gastrointestinal parasites. In this paper the available data on protective immunity against gastrointestinal nematodes, and especially Ostertagia ostertagi, in cattle are compared with the current knowledge of protective immune responses against gastrointestinal nematodes in rodent models and small ruminants. In contrast to the immune response in mice, which is controlled by T helper 2 (Th2) lymphocytes and results in mast cell- or goblet cell- mediated expulsion of adult worms, bovine immune responses to O. ostertagi do not show a clear Th2 cytokine profile, nor do they result in rapid expulsion of the parasite. The first manifestation of immunity to O. ostertagi in calves is a reduction of worm fecundity, possibly regulated by the local IgA response. Worm numbers are only reduced after a prolonged period of host–parasite contact, and there are indications that O. ostertagi actively suppresses the host's immune response. Until the mechanisms of protective immunity against O. ostertagi are revealed, the use of immunological parameters to estimate acquired immunity in cattle is based on their correlation with parasitological parameters and on extrapolation from rodent and small ruminant models. Assessing the resistance of calves against a challenge infection by means of parasitological parameters is probably still the most accurate way to measure acquired immunity against gastrointestinal nematodes.

scholarly journals Protective Immunity to Rotavirus Shedding in the Absence of Interleukin-6: Th1 Cells and Immunoglobulin A Develop Normally

2000 ◽  
Vol 74 (11) ◽  
pp. 5250-5256 ◽  
Author(s):  
John L. VanCott ◽  
Manuel A. Franco ◽  
Harry B. Greenberg ◽  
Steffanie Sabbaj ◽  
Baozhing Tang ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Protective Immunity ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Specific Response ◽  
T Helper 1 ◽  
Adult Mice ◽  
Iga Response ◽  
Antigen Presenting ◽  
Interferon Responses

ABSTRACT We investigated whether interleukin-6 (IL-6) was required for the development of immunoglobulin A (IgA)- and T-helper 1 (Th1)-associated protective immune responses to rotavirus by using adult IL-6-deficient mice [BALB/c and (C57BL/6 × O1a)F2 backgrounds]. Naive IL-6− mice had normal frequencies of IgA plasma cells in the gastrointestinal tract. Consistent with this, total levels of IgA in fecal extracts, saliva, and sera were unaltered. In specific response to oral infection with rhesus rotavirus, IL-6−and IL-6+ mice exhibited efficient Th1-type gamma interferon responses in Peyer's patches with high levels of serum IgG2a and intestinal IgA. Although there was an increase in Th2-type IL-4 in CD4+ T cells from IL-6− mice following restimulation with rotavirus antigen in the presence of irradiated antigen-presenting cells, unfractionated Peyer's patch cells failed to produce a significant increase in IL-4. Moreover, virus-specific IgG1 in serum was not significantly increased in IL-6− mice in comparison with IL-6+ mice. Following oral inoculation with murine rotavirus, IL-6− and IL-6+ mice mediated clearance of rotavirus and mounted a strong IgA response. When IL-6− and IL-6+ mice [(C57BL/6 × O1a)F2 background] were orally inoculated with rhesus rotavirus and later challenged with murine rotavirus, all of the mice maintained high levels of IgA in feces and were protected against reinfection. Thus, IL-6 failed to provide unique functions in the development of IgA-secreting B cells and in the establishment of Th1-associated protective immunity against rotavirus infection in adult mice.

scholarly journals A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow

Blood ◽  
2015 ◽  
Vol 125 (11) ◽  
pp. 1739-1748 ◽  
Author(s):  
Henrik E. Mei ◽  
Ina Wirries ◽  
Daniela Frölich ◽  
Mikael Brisslert ◽  
Claudia Giesecke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
B Cell ◽  
Plasma Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Healthy Human ◽  
Key Points

Key Points Healthy human BM is enriched for PC lacking CD19 that express a prosurvival and distinctly mature phenotype. CD19− PC resist mobilization into blood during immune responses after vaccination as well as B-cell depletion with rituximab.

scholarly journals Mucosal and Systemic Immune Responses in Patients with Diarrhea Due to CS6-Expressing Enterotoxigenic Escherichia coli

2007 ◽  
Vol 75 (5) ◽  
pp. 2269-2274 ◽  
Author(s):  
Firdausi Qadri ◽  
Tanvir Ahmed ◽  
Firoz Ahmed ◽  
M. Saruar Bhuiyan ◽  
Mohammad Golam Mostofa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Protein A ◽  
Enterotoxigenic Escherichia Coli ◽  
Severe Dehydration ◽  
Colonization Factor ◽  
Disease Spectrum ◽  
Iga Antibodies ◽  
Iga Antibody ◽  
Antibody Secreting Cells

ABSTRACTColonization factor CS6 expressed by enterotoxigenicEscherichia coli(ETEC) is a nonfimbrial polymeric protein. A substantial proportion of ETEC strains isolated from patients in endemic settings and in people who travel to regions where ETEC is endemic are ETEC strains expressing CS6, either alone or in combination with fimbrial colonization factor CS5 or CS4. However, relatively little is known about the natural immune responses elicited against CS6 expressed by ETEC strains causing disease. We studied patients who were hospitalized with diarrhea (n= 46) caused by CS6-expressing ETEC (ETEC expressing CS6 or CS5 plus CS6) and had a disease spectrum ranging from severe dehydration (27%) to moderate or mild dehydration (73%). Using recombinant CS6 antigen, we found that more than 90% of the patients had mucosal immune responses to CS6 expressed as immunoglobulin (IgA) antibody-secreting cells (ASC) or antibody in lymphocyte supernatant (ALS) and that about 57% responded with CS6-specific IgA antibodies in feces. More than 80% of the patients showed IgA seroconversion to CS6. Significant increases in the levels of anti-CS6 antibodies of the IgG isotype were also observed in assays for ASC (75%), ALS (100%), and serum (70%). These studies demonstrated that patients hospitalized with the noninvasive enteric pathogen CS6-expressing ETEC responded with both mucosal and systemic antibodies against CS6. Studies are needed to determine if the anti-CS6 responses protect against reinfection and if protective levels of CS6 immunity are induced by vaccination.

scholarly journals Local and Systemic Immune Responses to Rectal Administration of Recombinant Cholera Toxin B Subunit in Humans

2001 ◽  
Vol 69 (6) ◽  
pp. 4125-4128 ◽  
Author(s):  
Marianne Jertborn ◽  
Inger Nordström ◽  
Anders Kilander ◽  
Cecil Czerkinsky ◽  
Jan Holmgren
Keyword(s):  
Immune Responses ◽  
Cholera Toxin ◽  
Immunoglobulin A ◽  
Rectal Administration ◽  
Antibody Responses ◽  
Cholera Toxin B Subunit ◽  
Toxin B ◽  
Cholera Toxin B ◽  
B Subunit ◽  
Antibody Secreting Cells

ABSTRACT The induction of immune responses to rectally administered recombinant cholera toxin B subunit (CTB) in humans was studied. Three immunizations induced high levels of CTB-specific antibody-secreting cells, particular of the immunoglobulin A isotype, in both rectum and peripheral blood. Antitoxin antibody responses in rectal secretions and serum were also found.

scholarly journals T-Cell Immune Response Assessment as a Complement to Serology and Intranasal Protection Assays in Determining the Protective Immunity Induced by Acellular Pertussis Vaccines in Mice

2003 ◽  
Vol 10 (4) ◽  
pp. 637-642 ◽  
Author(s):  
C. M. Ausiello ◽  
R. Lande ◽  
P. Stefanelli ◽  
C. Fazio ◽  
G. Fedele ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Pertussis Toxin ◽  
Protective Immunity ◽  
T Cell Responses ◽  
Additional Tool ◽  
Cell Responses ◽  
T Cell Immune Responses ◽  
Ifn Γ

ABSTRACT The relative value of antibodies and/or T-cell immune responses to Bordetella pertussis antigens in the immunity induced by acellular pertussis (aP) vaccines is still an open issue, probably due to the incomplete knowledge on the mechanisms of protective immunity to pertussis. The relevance of T-cell immune responses in protection from pertussis has been demonstrated in murine and human models of infection; thus, in this study, the ability of different vaccine preparations of three component (pertussis toxin, filamentous hemagglutinin, and pertactin) aP vaccines to induce T-cell responses was investigated in mice. All vaccine preparations examined passed the immunogenicity control test, based on antibody titer assessment, according to European Pharmacopoeia standards, and protected mice from B. pertussis intranasal challenge, but not all preparations were able to prime T cells to pertussis toxin, the specific B. pertussis antigen. In particular, one vaccine preparation was unable to induce proliferation and gamma interferon (IFN-γ) production while the other two gave borderline results. The evaluation of T-cell responses to pertussis toxin antigen may provide information on the protective immunity induced by aP vaccines in animal models. Considering the critical role of the axis interleukin-12-IFN-γ for protection from pertussis, our results suggest that testing the induction of a key protective cytokine such as IFN-γ could be an additional tool for the evaluation of the immune response induced by aP vaccines.

scholarly journals Longitudinal monitoring of SARS-CoV-2-specific immune responses

2021 ◽  
Author(s):  
Heike Rebholz ◽  
Ralf J. Braun ◽  
Titas Saha ◽  
Oliver Harzer ◽  
Miriam Schneider ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Immunoglobulin G ◽  
Immunoglobulin A ◽  
Comprehensive View ◽  
Iga Antibodies ◽  
Specific Immunoglobulin ◽  
Second Peak

The Lower Austrian Wachau region was an early COVID-19 hotspot of infection. As previously reported, in June 2020, after the first peak of infections, we determined that 8.5% and 9.0% of the participants in Weissenkirchen and surrounding communities in the Wachau region were positive for SARS-CoV-2-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies, respectively. Here, we present novel data obtained eight months later (February 2021) from Weissenkirchen, after the second peak of infection, with 25.0% (138/552) and 23.6% (130/552) of participants that are positive for IgG and IgA, respectively. In participants with previous IgG/IgA positivity (June 2020), we observed a 24% reduction in IgG levels, whereas the IgA levels remained stable in February 2021. This subgroup was further analyzed for SARS-CoV-2-induced T cell activities. Although 76% (34/45) and 76% (34/45) of IgG positive and IgA positive participants, respectively, showed specific T cell activities, those were not significantly correlated with the levels of IgG or IgA. Thus, the analyses of antibodies cannot surrogate the measurement of T cell activities. For a comprehensive view on SARS-CoV-2-triggered immune responses, the measurement of different classes of antibodies should be complemented with the determination of T cell activities.

scholarly journals Memory persistence and differentiation into antibody-secreting cells accompanied by positive selection in longitudinal BCR repertoires

2022 ◽  
Author(s):  
Artem I. Mikelov ◽  
Evgeniia I. Alekseeva ◽  
Ekaterina A. Komech ◽  
Dmitriy B. Staroverov ◽  
Maria A. Turchaninova ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Inflammatory Diseases ◽  
Affinity Maturation ◽  
Memory B Cells ◽  
Immune Memory ◽  
Memory B Cell ◽  
Antibody Secreting Cells

B-cell mediated immune memory holds both plasticity and conservatism to respond to new challenges and repeated infections. Here, we analyze the dynamics of immunoglobulin heavy chain (IGH) repertoires of memory B cells, plasmablasts and plasma cells sampled several times during one year from peripheral blood of volunteers without severe inflammatory diseases. We reveal a high degree of clonal persistence in individual memory B-cell subsets with inter-individual convergence in memory and antibody-secreting cells (ASCs). Clonotypes in ASCs demonstrate clonal relatedness to memory B cells and are transient in peripheral blood. Two clusters of expanded clonal lineages displayed different prevalence of memory B cells, isotypes, and persistence. Phylogenetic analysis revealed signs of reactivation of persisting memory B cell-enriched clonal lineages, accompanied by new rounds of affinity maturation during proliferation to ASCs. Negative selection contributes to both, persisting and reactivated lineages, saving functionality and specificity of BCRs to protect from the current and future pathogens.

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