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Fulltext Epstein-Barr virus, the germinal centre and the development of Hodgkin's lymphoma

Mohamed G, Vrzalikova K, Cader FZ, Vockerodt M, Nagy E, Flodr P, et al.

J Gen Virol, 2014 Sep;95(Pt 9):1861-1869.
PMID: 24893782 DOI: 10.1099/vir.0.066712-0

The relationship between Epstein-Barr virus (EBV) and the germinal centre (GC) of the asymptomatic host remains an enigma. The occasional appearance of EBV-positive germinal centres in some patients, particularly those with a history of immunosuppression, suggests that EBV numbers in the GC are subject to immune control. The relationship, if any, between lymphoid hyperplasia with EBV-positive germinal centres and subsequent or concurrent lymphomagenesis remains to be clarified. As far as the development of EBV-associated Hodgkin's lymphoma is concerned, the suppression of virus replication, mediated by LMP1 on the one hand, and the loss of B-cell receptor signalling on the other, appears to be an important pathogenic mechanism. A further important emerging concept is that alterations in the microenvironment of the EBV-infected B-cell may be important for lymphomagenesis.

Matched MeSH terms: Receptors, Antigen, B-Cell/immunology
Fulltext RNA sequencing (RNA-Seq) of lymph node, spleen, and thymus transcriptome from wild Peninsular Malaysian cynomolgus macaque (Macaca fascicularis)

Ee Uli J, Yong CSY, Yeap SK, Rovie-Ryan JJ, Mat Isa N, Tan SG, et al.

PeerJ, 2017;5:e3566.
PMID: 28828235 DOI: 10.7717/peerj.3566

The cynomolgus macaque (Macaca fascicularis) is an extensively utilised nonhuman primate model for biomedical research due to its biological, behavioural, and genetic similarities to humans. Genomic information of cynomolgus macaque is vital for research in various fields; however, there is presently a shortage of genomic information on the Malaysian cynomolgus macaque. This study aimed to sequence, assemble, annotate, and profile the Peninsular Malaysian cynomolgus macaque transcriptome derived from three tissues (lymph node, spleen, and thymus) using RNA sequencing (RNA-Seq) technology. A total of 174,208,078 paired end 70 base pair sequencing reads were obtained from the Illumina Hi-Seq 2500 sequencer. The overall mapping percentage of the sequencing reads to the M. fascicularis reference genome ranged from 53-63%. Categorisation of expressed genes to Gene Ontology (GO) and KEGG pathway categories revealed that GO terms with the highest number of associated expressed genes include Cellular process, Catalytic activity, and Cell part, while for pathway categorisation, the majority of expressed genes in lymph node, spleen, and thymus fall under the Global overview and maps pathway category, while 266, 221, and 138 genes from lymph node, spleen, and thymus were respectively enriched in the Immune system category. Enriched Immune system pathways include Platelet activation pathway, Antigen processing and presentation, B cell receptor signalling pathway, and Intestinal immune network for IgA production. Differential gene expression analysis among the three tissues revealed 574 differentially expressed genes (DEG) between lymph and spleen, 5402 DEGs between lymph and thymus, and 7008 DEGs between spleen and thymus. Venn diagram analysis of expressed genes revealed a total of 2,630, 253, and 279 tissue-specific genes respectively for lymph node, spleen, and thymus tissues. This is the first time the lymph node, spleen, and thymus transcriptome of the Peninsular Malaysian cynomolgus macaque have been sequenced via RNA-Seq. Novel transcriptomic data will further enrich the present M. fascicularis genomic database and provide future research potentials, including novel transcript discovery, comparative studies, and molecular markers development.

Matched MeSH terms: Receptors, Antigen, B-Cell
Diffuse large B-cell lymphoma in Southeast Asian cohort: expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy

Masir N, Akhter A, Roshan TM, Florence CS, Abdul-Rahman F, Tumian NR, et al.

J Clin Pathol, 2019 Sep;72(9):630-635.
PMID: 31189540 DOI: 10.1136/jclinpath-2019-205837

AIMS: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia.
METHODS: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS).
RESULTS: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05).
CONCLUSIONS: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.

Matched MeSH terms: Receptors, Antigen, B-Cell/genetics*; Receptors, Antigen, B-Cell/immunology

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