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Review
. 2024 Mar 14;12(3):648.
doi: 10.3390/biomedicines12030648.

The Possible Role of Pathogens and Chronic Immune Stimulation in the Development of Diffuse Large B-Cell Lymphoma

Lajos Gergely  1 , Miklos Udvardy  1 , Arpad Illes  1
Affiliations
Review

The Possible Role of Pathogens and Chronic Immune Stimulation in the Development of Diffuse Large B-Cell Lymphoma

Lajos Gergely et al. Biomedicines. .

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. The disease is very heterogeneous, with distinct genetic alterations in subtypes. The WHO 2022 5th edition classification identifies several minor groups of large B-cell lymphoma where the pathogenetic role of viruses (like EBV and HHV-8) is identified. Still, most cases fall into the group of DLBCL not otherwise specified (NOS). No review focuses only on this specific lymphoma type in the literature. The pathogenesis of this entity is still not fully understood, but several viruses and bacteria may have a role in the development of the disease. The authors review critical pathogenetic events in the development of DLBCL (NOS) and summarize the data available on several pathogenetic viruses and bacteria that have a proven or may have a potential role in the development of this lymphoma type. The possible role of B-cell receptor signaling in the microenvironment is also discussed. The causative role of the Epstein-Barr virus (EBV), human herpesvirus-8 (HHV-8), Hepatitis C virus (HCV), human immunodeficiency virus (HIV), Hepatitis B virus (HBV), and other viruses are explored. Bacterial infections, such as Helicobacter pylori, Campylobacter jejuni, Chlamydia psittaci, Borrelia burgdorferi, and other bacteria, are also reviewed.

Keywords: B-Cell Receptor; DLBCL; EBV; HBV; HCV; HHV8; HIV; campylobacter; helicobacter; microenvironment; pathogenesis; pathogens; retrovirus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of Toll-like-receptor (TLR) pathways. The basic elements of the mentioned TLR signaling pathways are shown in the figure. The top row lists the recognized damage-associated molecular patterns (DAMPs). Below is the corresponding TLR. The main signaling molecules are listed as the most important terminal complex. CpG—cytosine-phosphate-guanine dideoxynucleotide motif, ssRNA—single-stranded ribonucleic acid, LPS—lipopolyscaccharide, dsRNA—double-stranded ribonucleic acid, MYD88—myeloid differentiation primary response 88, TRIF—TIR domain-containing adaptor protein, IRAK—interleukin-1 receptor-associated kinase, TRAF—tumor necorsis factor-associated factor, IRF—interferon regulatory factor, p38—p38-mitogen-activated protein kinase, ERK—extracellular signal-regulated kinase, NfKappa-B—nuclear factor kappaB.
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