Impact of B cell/lymphoid stromal cell crosstalk in B-cell physiology and malignancy

Abstract

Highlights-Lymphoid stromal cells form a heterogeneous and plastic cell compartment -Follicular and extrafollicular stromal cells contribute to normal B-cell activation -FL-CAFs exhibit specific phenotypic and transcriptomic features -FL B cells and their immune microenvironment trigger FL-CAF differentiation -FL-CAFs support directly malignant B-cell growth and organize tumor cell niche Abstract Stromal cells have been considered for a long time essentially as a structural component organizing tissue architecture, including those of secondary lymphoid organs. More recently, highly specialized stromal cell subsets were shown to differentially organize immune cell recruitment, survival, and differentiation within lymph nodes. In particular, mature B cells interact with different lymphoid stromal cell networks through bidirectional interactions involving cell-cell contact and soluble factors. Follicular lymphoma (FL) is the paradigm of a B-cell malignancy dependent on a lymphoid-like microenvironment supporting tumor cell growth, drug resistance, and clonal evolution. This review provides an overview of our current knowledge of lymphoid stromal cell heterogeneity and functions in normal B-cell activation. In addition, we also depict the dynamic and plasticity of FL cancer-associated fibroblasts, the mechanisms underlying their key role within FL permissive niches, and their potential as therapeutic targets in this still fatal malignancy.

Integrative Analysis of Cell Crosstalk within Follicular Lymphoma Cell Niche: Towards a Definition of the FL Supportive Synapse

“…As an example, we demonstrated that the introduction of n -glycosylation acceptor sites harboring unusual high-mannose oligosaccharides in FL BCR triggers the interaction of malignant B cells with DC-SIGN-expressing tumor-infiltrating macrophages resulting in BCR-dependent FL B cell activation [ 11 ]. In addition, malignant FL B cells display a substantial dependency on their microenvironment organized as specific supportive cell niches providing survival and proliferation signals (reviewed in [ 12 , 13 ]). Composition and spatial organization of the FL niches have a huge impact on patient prognosis, as initially described by Dave et al [ 14 ].…”

Developing a 3D B Cell Lymphoma Culture System to Model Antibody Therapy

“…Under normal conditions, a clear inter-relationship exists between B cells and the fibro-reticular network, (FRN) of secondary lymphoid organs. This is also observed in pathological conditions ( 11 ), particularly in lymphoma and during the formation of tertiary lymphoid structures in the context of inflammation ( 12 ). In the case of FL, cross talk between tumor cells and cells of the local FRN drives their differentiation into tumor-supporting lymphoid stroma ( 13 ).…”

Follicular Lymphoma Microenvironment: An Intricate Network Ready for Therapeutic Intervention

“…They organize and regulate immune cell trafficking, differentiation, and migration of T cells through an IL-4/CXCL12 communication axis with T FH , among other signals, and secretion of additional chemokines such as CCL19 and CCL21. FRC also plays a direct role in B malignant cells' activation and survival through BAFF signaling [16][17][18][19].…”