The invention provides a novel cell line development method useful to screen for recombinant protein production. The method utilizes a membrane-anchored reporter or an intracellular reporter residing in the expression vector for a gene of interest to facilitate initial cell selection by FACS or MACS. A switching mechanism can be used to delete the reporter from the chromosome by providing an appropriate DNA recombinase, which turns the selected cells into production cells that secrete the protein of interest without co-expression of the reporter.