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

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