Suppression of Class Switch Recombination to IgA by RASA2 and RASA3 through Inhibition of TGF-β Signaling.

Abs play a pivotal role in adaptive immunity by binding to pathogens and initiating immune responses against infections. Processes such as somatic hypermutation and class switch recombination (CSR) enhance Ab affinity and effector functions. We previously carried out a CRISPR/Cas9 screen in the CH12F3-2 (CH12) lymphoma B cell line to identify novel factors involved in CSR.

Arf1-PI4KIIIβ positive vesicles regulate PI(3)P signaling to facilitate lysosomal tubule fission.

Formation and fission of tubules from autolysosomes, endolysosomes, or phagolysosomes are required for lysosome reformation. However, the mechanisms governing these processes in these different lysosomal organelles are poorly understood. Thus, the role of phosphatidylinositol-4-phosphate (PI(4)P) is unclear as it was shown to promote the formation of tubules from phagolysosomes but was proposed to inhibit tubule formation on autolysosomes because the loss of PI4KIIIβ causes extensive lysosomal tubulation.

Reactive oxygen species prevent lysosome coalescence during PIKfyve inhibition.

Lysosomes are terminal, degradative organelles of the endosomal pathway that undergo repeated fusion-fission cycles with themselves, endosomes, phagosomes, and autophagosomes. Lysosome number and size depends on balanced fusion and fission rates. Thus, conditions that favour fusion over fission can reduce lysosome numbers while enlarging their size.

IKKε and TBK1 in diffuse large B-cell lymphoma: A possible mechanism of action of an IKKε/TBK1 inhibitor to repress NF-κB and IL-10 signalling.

The IKK-related kinases, IKKε and TBK1, have essential roles in innate immunity in part through modifying MYD88 signalling from the Toll-like receptors to regulate NF-κB signalling. We investigated the expression and function of IKKε and TBK1, in diffuse large B-cell lymphoma (DLBCL). DLBCL cell lines and patient-derived xenografts were used to determine their sensitivity to IKKε and TBK1 inhibitors.

Multiple mutations at exon 2 of RHOA detected in plasma from patients with peripheral T-cell lymphoma.

The mutational landscape of peripheral T-cell lymphoma (PTCL) is being revealed through sequencing of lymph node samples, but there has been little work on the mutational load that is present in cell-free DNA (cfDNA) from plasma. We report targeted sequencing of cfDNA from PTCL patients to demonstrate c.50G>T (p.

Structural and diffusion weighted MRI demonstrates responses to ibrutinib in a mouse model of follicular helper (Tfh) T-cell lymphoma.

Recent analyses of the genetics of peripheral T-cell lymphoma (PTCL) have shown that a large proportion of cases are derived from normal follicular helper (Tfh) T-cells. The sanroque mouse strain bears a mutation that increases Tfh cell number and heterozygous animals (Roquinsan/+) develop lymphomas similar to human Tfh lymphoma. Here we demonstrate the usefulness of Roquinsan/+ animals as a pre-clinical model of Tfh lymphoma.

Interleukin-2-inducible T-cell kinase inhibitors modify functional polarization of human peripheral T-cell lymphoma cells.

ITK inhibitors perturb functional changes due to polarizing culture conditions in normal human tonsil CD4 T cells. Primary human PTCL cells alter their functional properties in culture and ITK inhibitors modify these changes.

Comparison of interleukin-2-inducible kinase (ITK) inhibitors and potential for combination therapies for T-cell lymphoma.

Patients with peripheral T-cell lymphomas generally have poor clinical outcomes with conventional chemotherapy. Recent advances have demonstrated that a large subgroup of PTCL are derived from follicular helper (Tfh) T-cells. These cases show a characteristic pattern of gene expression, which includes high-level protein expression of interleukin-2-inducible kinase (ITK).

PD1 cells associate with clusters of proliferating B-cells in marginal zone lymphoma.

Background: Abnormally sustained immune reactions drive B-cell proliferation in some cases of marginal zone lymphoma but the CD4 T-cell subsets, which are likely to contribute to the B-cell responses in the tumour microenvironment, are not well characterised and neither has the spatial distribution of the different subsets in involved lymph nodes been investigated.

Methods: Employing a workflow of multiplex semi-automated immunohistochemistry combined with image processing we investigated association between infiltrating T-cells and proliferating lymphoma B-cells.

Results: Both total numbers of activating follicular helper (Tfh) cells (defined by high expression of PD1) and suppressive regulatory (Treg) T-cells (defined by FOXP3 expression) and the Tfh:Treg ratio, assessed over relatively large areas of tissue, varied among cases of marginal zone lymphoma.