Fibroblastic Reticular Cells Modulate Tumor Microenvironment of Chronic Lymphocytic Leukemia (CLL)

Overview

In patients with Chronic Lymphocytic Leukemia (CLL), there is an overgrowth of leukemic B -lymphocytes. This proliferation of B -cells requires inputs from the external microenvironment, which provides soluble molecules as well as physical interaction necessary for survival and proliferation. Studies have shown that the lymph nodes are one of such microenvironments. However, the specific interaction between lymph nodes and leukemic B -cell has not been elucidated. This study examines how fibroblastic reticular cells (FRCs) from the lymph nodes, and IL4 secreted by T-cells affect the proliferation and signaling of leukemic Bcells. When leukemic Bcells were co -cultured with FRCs, there was a significant increase in the number of leukemic Bcells. Moreover, the expression of CLECL1 surface protein is further increased on B -cells. Using recombinant CLECL1 protein, it was demonstrate d that IL4 cytokine production increases in both naive T-cells and Th2 cells. In the presence of IL4, the level of proliferation of CLL B-cells is amplified. IL4 can also increase the expression of lymphotoxin (a cytokine) in B -cells and the lymphotoxin r eceptor on FRC. The expression of lymphotoxin is repressed in the presence of FRC. The expression of lymphotoxin in B -cells correlates with high levels of the adipocytokine CXCL13 by FRC. High level of CXCL13 subsequently correlates with reduced expressio n of CXCR5, which is required for B -cell migration and localization to the FRCs and is believed to play an important role in CLL cell proliferation. This study demonstrates that interactions with FRCs and IL4 is essential and necessary for CLL progression. The Effect of Food Deprivation on the Memory of Drosophila melanogaster Larvae Kate Santoli, Gabriella Ramirez, and Katy Gottlieb Lynbrook Senior High School, Lynbrook NY