fig2

Figure 2. Features of NHL EVs as biomarkers in blood include exo-microRNA, exo-messenger RNA, and exo-proteins, such as CD19, CD20, CD22, CD24, CD37, MHC class I molecules, MHC class II molecules, and immunoglobulins^{[17,41,48,51,55,56]}. (A) NHL B cell with biomarker features: Most forms of non-Hodgkin B cell lymphoma originate in the lymph nodes during B cell maturation^[45-47]. (B) NHL B cell ectosome biogenesis: Outward budding pinches off to release contents of the cell as cargo packaged within the cell’s membrane and surface proteins as EV microvesicles^[13,14,41]. (C) NHL B cell exosome biogenesis: Through the endosomal sorting complexes required for transport (ESCRT) pathway, cell membrane surface proteins (such as CD19 or CD20) invaginate into the cell. Within multivesicular bodies, intraluminal vesicles form with these surface membrane proteins to carry contents of the NHL B cells, such as RNA and proteins. These vesicles are expelled from the cell as EV exosomes^[13,14,41]. (D) NHL B cell apoptotic body biogenesis: Apoptosis fragments into newly formed EV apoptotic bodies, with the membrane and its surface proteins enveloping cell contents of RNA and proteins^[13,14,41]. (E) Blood vessel with heterogeneous circulating NHL EVs: Heterogeneous subpopulations of NHL EVs are released into environs of the NHL cells and into the bloodstream. Varying in size, they carry diverse contents internally with various RNA and proteins and externally with differing antigens, MHC class molecules, and immunoglobulins^{[17,41,48,51,55,56]} (images in the figure are not drawn to exact scale).