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    Home > Active Ingredient News > Immunology News > A&R: Effects of clonal expansion of PD-1highCXCR5-CD4+ peripheral T helper cells on articular B cell differentiation in patients with antinuclear antibody-positive juvenile idiopathic arthritis

    A&R: Effects of clonal expansion of PD-1highCXCR5-CD4+ peripheral T helper cells on articular B cell differentiation in patients with antinuclear antibody-positive juvenile idiopathic arthritis

    • Last Update: 2022-02-18
    • Source: Internet
    • Author: User
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    Objective: Antinuclear antibody (ANA) -positive juvenile idiopathic arthritis (JIA) is characterized by synovial B cell hyperactivity, but the exact role of CD4+ T cells in promoting local B cell activation is unclear
    .


    The SF CD4+ T helper cell pool in patients with ANA -positive JIA was previously found to be particularly enriched in IL-21- secreting cells, and CD21low / –CD11c + DN B cells accumulated in the joints of these patients .


    Objective: Antinuclear antibody (ANA) -positive juvenile idiopathic arthritis (JIA) is characterized by synovial B cell hyperactivity, but the exact role of CD4+ T cells in promoting local B cell activation is unclear


    Methods: Flow cytometry was performed to compare the phenotype and cytokine patterns of PD-1 high CD4+ T high cells in the synovial fluid (SF) of JIA patients and T follicular helper cells in the tonsils of control individuals .
    TCRVB TCRVB next- generation sequencing was used to analyze T cell subsets for signs of clonal expansion .
    The functional effects of these T cell subsets on B cells were examined in in vitro co-cultures (flow cytometry to measure B cell differentiation, ELISA to measure total IgG concentration in the medium ) .

    Results: Multidimensional flow cytometry revealed that interleukin 21 ( IL -21) and interferon - γ (IFNγ ) co-expressed PD-1 high CXCR5 – HLA – DR+CD4+ in the joints of ANA -positive JIA patients Expansion of T cells .


    These T cells showed signs of clonal expansion with restricted T cell receptor clonotypes .
    This phenotype resembles peripheral T helper (Tph) cells with an extrafollicular chemokine receptor pattern and high T-bet and B lymphocyte-induced mature protein 1 expression, but low B - cell lymphoma 6 expression .
    SF Tph cells provide IL-21 and IFN by γ, differentiates B cells to the CD21 low/ CD11c+ phenotype in vitro


    Results: Multidimensional flow cytometry revealed that interleukin 21 ( IL -21) and interferon - γ (IFNγ ) co-expressed PD-1 high CXCR5 high – HLA – DR+ in the joints of ANA -positive JIA patients Expansion of CD4+ T cells .
    These T cells showed signs of clonal expansion with restricted T cell receptor clonotypes .
    This phenotype resembles peripheral T helper (Tph) cells with an extrafollicular chemokine receptor pattern and high T-bet and B lymphocyte-induced mature protein 1 expression, but low B - cell lymphoma 6 expression .
    SF Tph cells provide IL-21 andIFNγ , differentiated B cells to CD21 low/ low/ – CD11c+ phenotype in vitro


         Conclusions: Clonally expanded CD4+ Tph cells accumulate in the joints of ANA -positive JIA patients, especially promoting CD21 low/ low/ – CD11c+ DN B cell differentiation


    Source:

    Fischer, J.


    , Dirks, J.
    , Klaussner, J.
    , Haase, G.


    Fischer, J.
    , Dirks, J.
    , Klaussner, J.
    , Haase, G.
    , Holl-Wieden, A.
    , Hofmann, C.
    , Hackenberg, S.
    , Girschick, H.
    and Morbach, H.
    (2022), Effect of Clonally Expanded PD-1 high high CXCR5–CD4+ Peripheral T Helper Cells on B Cell Differentiation in the Joints of Patients With Antinuclear Antibody–Positive Juvenile Idiopathic Arthritis.
    Arthritis Rheumatol, 74: 150-162.
      https://doi.
    org /10.
    1002/art.
    41913 leave a message here
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