Direct Phenotypical and Functional Dysregulation of Primary Human B Cells by Human Immunodeficiency Virus (HIV) Type 1 In Vitro
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{"title"=>"Direct phenotypical and functional dysregulation of primary human b cells by human immunodeficiency virus (HIV) type 1 in vitro", "type"=>"journal", "authors"=>[{"first_name"=>"Ana Judith", "last_name"=>"Perisé-Barrios", "scopus_author_id"=>"55305697100"}, {"first_name"=>"María Ángeles", "last_name"=>"Muñoz-Fernandez", "scopus_author_id"=>"25931106800"}, {"first_name"=>"Marjorie", "last_name"=>"Pion", "scopus_author_id"=>"6603410241"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"22768302", "doi"=>"10.1371/journal.pone.0039472", "sgr"=>"84874287754", "isbn"=>"1932-6203", "scopus"=>"2-s2.0-84874287754", "issn"=>"19326203", "pui"=>"365201656"}, "id"=>"bff19b3b-8387-316d-b057-b1eb043511da", "abstract"=>"BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation.\\n\\nMETHODS/PRINCIPAL FINDINGS: We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and phenotype of primary B cells in vitro. Moreover, we examined expression of activation-induced cytidine deaminase (AID) mRNA that is responsible for class switch recombination (CSR) and somatic hypermutation (SHM). Here, we report that changes observed in cellular proliferation, phenotypes and activation of B cells could be caused by direct contact between HIV-1 particles and primary B cells in vitro. Finally, direct HIV-1-derived B cells activation led to the increase of AID mRNA expression and its subsequent CSR function was detected in vitro.\\n\\nCONCLUSION/SIGNIFICANCE: We showed that HIV-1 could directly induce primary B cells dysregulation triggering phenotypical and functional abilities of B cells in vitro that could explain in some extent early B-cell abnormalities in HIV disease.", "link"=>"http://www.mendeley.com/research/direct-phenotypical-functional-dysregulation-primary-human-b-cells-human-immunodeficiency-virus-hiv-2", "reader_count"=>14, "reader_count_by_academic_status"=>{"Researcher"=>4, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>4, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>11, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"South Africa"=>1, "Spain"=>2}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/319555", "https://ndownloader.figshare.com/files/319575", "https://ndownloader.figshare.com/files/319618", "https://ndownloader.figshare.com/files/319641", "https://ndownloader.figshare.com/files/319685"], "description"=>"<div><h3>Background</h3><p>Human immunodeficiency virus type 1 (HIV-1) induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation.</p> <h3>Methods/Principal Findings</h3><p>We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and phenotype of primary B cells <em>in vitro</em>. Moreover, we examined expression of activation-induced cytidine deaminase (AID) mRNA that is responsible for class switch recombination (CSR) and somatic hypermutation (SHM). Here, we report that changes observed in cellular proliferation, phenotypes and activation of B cells could be caused by direct contact between HIV-1 particles and primary B cells <em>in vitro</em>. Finally, direct HIV-1-derived B cells activation led to the increase of AID mRNA expression and its subsequent CSR function was detected <em>in vitro</em>.</p> <h3>Conclusion/Significance</h3><p>We showed that HIV-1 could directly induce primary B cells dysregulation triggering phenotypical and functional abilities of B cells <em>in vitro</em> that could explain in some extent early B-cell abnormalities in HIV disease.</p> </div>", "links"=>[], "tags"=>["phenotypical", "dysregulation", "cells", "immunodeficiency"], "article_id"=>123082, "categories"=>["Cancer", "Immunology"], "users"=>["Ana Judith Perisé-Barrios", "María Ángeles Muñoz-Fernandez", "Marjorie Pion"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039472.s001", "https://dx.doi.org/10.1371/journal.pone.0039472.s002", "https://dx.doi.org/10.1371/journal.pone.0039472.s003", "https://dx.doi.org/10.1371/journal.pone.0039472.s004", "https://dx.doi.org/10.1371/journal.pone.0039472.s005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Direct_Phenotypical_and_Functional_Dysregulation_of_Primary_Human_B_Cells_by_Human_Immunodeficiency_Virus_HIV_Type_1_In_Vitro_/123082", "title"=>"Direct Phenotypical and Functional Dysregulation of Primary Human B Cells by Human Immunodeficiency Virus (HIV) Type 1 <em>In Vitro</em>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-07-02 00:51:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/614706"], "description"=>"<p>B cells survival (A) and proliferation (B) were followed in <i>vitro</i>. (A) B cells were non-treated (NT) or treated with HIV<sub>NL4-3</sub> at 25 ng or 125 ng of p24<sup>gag</sup>, with 125 ng of p24<sup>gag</sup> boiled HIV<sub>NL4-3</sub>, with CD40L/IL-4or with LPS/IL-4. After 1, 4 and 6 days of culture, cells were collected and labeled with 7AAD, % of living cells were quantified in 7AAD negative population and % of cell survival was calculated as  =  (treated living cells / NT living cell at day 1 *100). (+SD; * = p<0.05 for both HIV-treatment conditions, LPS/IL-4 and CD40L/IL-4 conditions in comparison to NT condition)(B) After 1, 3 or 6 days post-treatment, percentage of proliferation was detected in CFSE-labeled B cells as the percent of B cells that lost their CFSE staining (See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039472#pone.0039472.s002\" target=\"_blank\">Figure S2</a>). (+SD; * = p<0.05 for both HIV-treatment conditions in comparison to NT condition). Mean of 7 experiments (125ng of p24<sup>gag</sup>, 125ng of p24<sup>gag</sup> boiled HIV<sub>NL4-3</sub> or LPS/IL-4 condition), of 5 experiments (CD40L/IL-4 condition) or 12 experiments (NT or 25 ng of p24<sup>gag</sup> conditions) shown.</p>", "links"=>[], "tags"=>["cells"], "article_id"=>285204, "categories"=>["Cancer", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Ana Judith Perisé-Barrios", "María Ángeles Muñoz-Fernandez", "Marjorie Pion"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039472.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_B_cells_survival_and_proliferation_/285204", "title"=>"B cells survival and proliferation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-02 01:26:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/614816"], "description"=>"<p>(A) Histogram plots of CD71 (left panel) and CD69 (right panel) expression markers at the surface of B-cell. (B) B cells were NT or treated with 25 ng and 125 ng of p24<sup>gag</sup> of HIV<sub>NL4-3</sub>, with 125 ng of p24<sup>gag</sup> of boiled-HIV<sub>NL4-3</sub>, with LPS/IL-4, mock-treated or treated with CD40L/IL-4. At day 1 (grey bars) or day 4 (black bars) post-treatment, CD71 and CD69 surface markers were followed by flow cytometry. Mean of 7 individuals donors excepted for mock and CD40L/IL-4 conditions (3 individuals donors) (+SD; * = p<0.05 in comparison to NT for day 1 or 4 post-treatment). Mock corresponded to the supernatant of MT2 non-infected cells. (C) B cells were NT or treated with 125 ng of p24<sup>gag</sup> of HIV<sub>NL4-3</sub>, with 125 ng of p24<sup>gag</sup> of HIV<sub>NL4-3</sub> treated with anti-HIV serum (Vol/Vol), mock-treated/anti-HIV serum or treated with LPS/IL-4. At day 1 post-treatment percentage of CD71 and CD69 were followed by flow cytometry. Mean of 3 individuals donors is represented (± SD; * = p<0.05).</p>", "links"=>[], "tags"=>["activation", "markers"], "article_id"=>285317, "categories"=>["Cancer", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Ana Judith Perisé-Barrios", "María Ángeles Muñoz-Fernandez", "Marjorie Pion"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039472.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_activation_markers_on_B_cells_/285317", "title"=>"Expression of activation markers on B cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-02 01:28:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/614887"], "description"=>"<p>(A)AID mRNA expression was quantified at 24 h post treatment in B cells. NT or treated B cells were cultured <i>in vitro</i> and mRNA was extracted and AID mRNA expression was quantified by real-time PCR. Fold increase was calculated as ratio of AID mRNA expression in comparison to NT condition. Each grey dot represents one experiment. Black bar represent average fold increase. (* = p<0.05). IgG (B), IgA (C) and IgE (D) production were quantified in cell culture supernatant by ELISA kit. (B) Mean of 10 experiments was represented (+SD). (C, D) Only experiments with detectable level of IgA or IgE was shown where each bar represent the result obtained for one individual donor. (ND: not determined).</p>", "links"=>[], "tags"=>["mrna", "cells", "igs"], "article_id"=>285379, "categories"=>["Cancer", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Ana Judith Perisé-Barrios", "María Ángeles Muñoz-Fernandez", "Marjorie Pion"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039472.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AID_mRNA_expression_in_B_cells_and_Igs_production_/285379", "title"=>"AID mRNA expression in B cells and Igs production.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-02 01:29:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/614950"], "description"=>"<p>(A) NT or treated B cells were cultured during 5 days. Intracellular CD19, IgM, IgD (A), IgG, IgA or IgE (B) markers were followed by flow cytometry. (A) IgD and IgM expression levels were followed in CD19+ population by percentage of positive cells for these markers *MFI of the same both markers ( = iMFI; integrated MFI). Mean of 5 individual donors (+SEM; * = p<0.05). (B) IgG, IgA and IgE expression levels were followed in CD19+ population by percentage of positive cells for each marker. Mean of 5 individual donors for IgG and IgA and 3 individual donors for IgE (+SEM; * = p<0.05).</p>", "links"=>[], "tags"=>["intracellular", "labeling", "vitro"], "article_id"=>285445, "categories"=>["Cancer", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Ana Judith Perisé-Barrios", "María Ángeles Muñoz-Fernandez", "Marjorie Pion"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039472.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Class_switch_detected_by_intracellular_labeling_in_in_vitro_B_cells_/285445", "title"=>"Class switch detected by intracellular labeling in in vitro B cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-07-02 01:30:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/615008"], "description"=>"<p>Expression of cell surface markers and B-cell subpopulations size on B cells at 4 days post-treatment. Average percentage of cell surface markers and B-cell subpopulations size on NT B cells or treated with 125 ng of p24<sup>gag</sup> of HIV<sub>NL4-3</sub>, Mock, boiled-HIV<sub>NL4-3</sub>, LPS/IL-4 and CD40L/IL-4 after 4 days of treatment. Results obtained from at least 4(<sup>a</sup>), 6 (<sup>b</sup>), 7 (<sup>c</sup>), 8 (<sup>d</sup>), 10 (<sup>e</sup>), and 12 (<sup>f</sup>) individual donors (±SEM). NT for non-treated B cells, ND for Non-Determined (*; p<0.05 in comparison to NT).</p>", "links"=>[], "tags"=>["subpopulations", "4d"], "article_id"=>285506, "categories"=>["Cancer", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Ana Judith Perisé-Barrios", "María Ángeles Muñoz-Fernandez", "Marjorie Pion"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0039472.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_B_cell_subpopulations_after_4d_of_HIV_NL4_3_treatment_/285506", "title"=>"B-cell subpopulations after 4d of HIV<sub>NL4-3</sub> treatment.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-07-02 01:31:46"}

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Relative Metric

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