Germinal Center Cells Turning to the Dark Side: Neoplasms of B Cells, Follicular Helper T Cells, and Follicular Dendritic Cells

Abstract

Gaining knowledge of the neoplastic side of the three main cells—B cells, Follicular Helper T (Tfh) cells, and follicular dendritic cells (FDCs) —involved in the germinal center (GC) reaction can shed light toward further understanding the microuniverse that is the GC, opening the possibility of better treatments. This paper gives a review of the more complex underlying mechanisms involved in the malignant transformations that take place in the GC. Whilst our understanding of the biology of the GC-related B cell lymphomas has increased—this is not reviewed in detail here—the dark side involving neoplasms of Tfh cells and FDCs are poorly studied, in great part, due to their low incidence. The aggressive behavior of Tfh lymphomas and the metastatic potential of FDCs sarcomas make them clinically relevant, merit further attention and are the main focus of this review. Tfh cells and FDCs malignancies can often be misdiagnosed. The better understanding of these entities linked to their molecular and genetic characterization will lead to prediction of high-risk patients, better diagnosis, prognosis, and treatments based on molecular profiles.

Tertiary lymphoid structures: Associated multiple immune cells and analysis their formation in hepatocellular carcinoma

“…30 Follicular dendritic cells and follicular helper T cells work together on B cells to further differentiate into plasma cells, which in turn produce antibodies to kill tumor cells. 31,32 Moreover, follicular dendritic cells can concentrate antigens and retain them on the cell surface for several weeks to several years. After B cells recognize antigens retained on the surface of follicular dendritic cells, somatic high-frequency mutations can occur, resulting in the diversity of antibodies.…”

“…Dendritic cells are one of the important sources of PD‐L1, and inhibition of PD‐L1 expression in dendritic cells can greatly promote CD8+ T cell response and inhibit tumor cell growth 30 . Follicular dendritic cells and follicular helper T cells work together on B cells to further differentiate into plasma cells, which in turn produce antibodies to kill tumor cells 31,32 . Moreover, follicular dendritic cells can concentrate antigens and retain them on the cell surface for several weeks to several years.…”

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

“…GCs are transient microstructures located in the center of B-follicles (for example in lymph nodes) where antigen-driven somatic hypermutation occurs. Moreover, GCs are the site of generation of affinity-matured plasma cells and memory B-cells capable of mediating long-term protective immunity in response to signals received by receptors [ 84 ]. For the scope of this review, it is also important to emphasize that B-cell receptor (BCR) signaling plays a role of the utmost importance in the survival of GC B-lymphocytes [ 85 ].…”

“…Overall, all of these findings highlight the key roles played by GSK-3β in the physiology of GC B-cells, including those committed to plasma cell differentiation. They are also intriguing in light of the involvement of GSK3-β in B-cell NHLs which mostly derive from GCs, as we will see in this article [ 84 ].…”

Editorial: New Insights Into the Complexity of Tumor Immunology in B-Cell Malignancies: Disease Biology and Signaling

“…In a focused review ( 10 ), Oppezzo, Navarrete and Chiorrazi explained the detrimental role of AID in leukemogenesis and disease progression by its “off-target” mutagenic activity, and also how AID is regulated in the lymph node microenvironment. In a mini review ( 11 ), Munguia-Fuentes, Maqueda-Alfaro, Yam-Puc and colleagues described the microenvironment of lymphoid tissue germinal centers where B cells undergo antigen-driven somatic hypermutations, a mechanism that is associated with malignant transformation.…”