Abstract A065: Oscillatory genes in lymphocyte retention and egress

The adaptive immune system attacks cancer cells by initiating immune responses in lymphoid organs and egressing of activated effector cells into circulation to reach the tumor. Several G protein-coupled receptors have been reported to recruit lymphocytes to the lymphoid organ or to promote exit. However, how these signals crosstalk to ensure efficient lymphocyte recruitment and transit is not well understood. To further define how cell transit through the lymphoid tissue is controlled, we designed two parallel RNAseq to identify novel regulators for lymphocyte transit. We compared the transcriptome of naive B cells from the blood and peripheral lymph node. Also, by utilizing photoconvertible proteins, we isolated naive B cells that newly enter the lymphoid organ and those that have been dwelling for several hours. We identified multiple genes whose transcript levels were correlated with lymphoid dwelling time. One of the genes, KLF11, encoding a transcription factor, is expressed more highly in the blood than in the lymph node, and the expression decreases with the dwelling time in the lymphoid organ. Analysis of the KLF11 knock-out mouse identified strong lymphocyte transit and developmental defects, but we found the strong phenotypes segregated independently of the KLF11 knock-out allele. The phenotypes were the result of a mutated DOCK2 allele in the commercial B6 background. We have now generated a KLF11 knock-out with wildtype DOCK2. The progress of characterizing the function of KLF11 in lymphocyte recruitment and egress will be reported. Citation Format: Hsin Chen, Timothy Schmidt, Ying Xu, Erick Lu, Jason G. Cyster. Oscillatory genes in lymphocyte retention and egress [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A065.