This 19-parameter, 18-color flow cytometry panel was designed and optimized to enable the comprehensive and simultaneous immunophenotyping of distinct T-cell, B-cell, and antibody secreting cell (ASC) subsets within murine tissues (Table 1). Cellular populations identified by using this OMIP include two major subsets of B-cells (memory and activated), two ASC subsets (plasma cells and plasmablasts), and seven major subsets of CD4+ T-cells (naïve, central memory, effector memory, helper, regulatory, follicular helper, and follicular regulatory). Staining was performed on freshly isolated splenocytes from 21-day-old BALB/c mice, however, due to the omission of mouse strain-specific markers, this OMIP can be implemented across a range of murine models where in-depth immunophenotyping of the diverse repertoire of T-cell, B-cell, and ASC populations is required.