The present application provides a group of human immortalized B lymphocyte cell lines and use thereof, and specifically provides a combination of four closely related immortalized lymphocyte cell lines. The combination can be used as a reference substances for measuring the performance of a detection platform. When the four closely related immortalized lymphocyte cell lines are used as reference substances for epigenome, transcriptome, proteome, and metabolome, an intrinsic magnitude difference gradient can be formed to evaluate the sensitivity of histological detection.