Identification and characterization of B220(+)/B220(−) subpopulations in murine Gr1(+)CD11b(+) cells during tumorigenesis

Although all murine MDSCs are defined as Gr1(+)CD11b(+), their true immunophenotype remains elusive. In this study, we found murine Gr1(+)CD11b(+) cells can be divided into two subsets: Gr1(+)CD11b(+)B220(−) and Gr1(+)CD11b(+)B220(+), especially in the spleen tissues. Unlike the dominant B220(−) subset, the B220(+) subpopulation was not induced by tumor in vivo. Moreover, Gr1(+)CD11b(+)B220(+) cells from tumor-bearing mice spleens were unable to induce arginase 1 and inducible nitric oxide synthase expression, inhibit T cell proliferation, or promote tumor growth in primary tumor site. Nevertheless, these cells suppressed tumor metastasis in vivo and reduced cancer cell motility in vitro, while Gr1(+)CD11b(+)B220(−) cells from tumor-bearing mice spleens promoted tumor metastasis and enhanced cancer cell motility. Furthermore, both the polymorphonuclear (PMN-MDSCs) and monocytic MDSCs (Mo-MDSCs) could be further divided into B220(−) and B220(+) subsets; interestingly, tumor only induced the expansion of B220(−) PMN-MDSCs and B220(−) Mo-MDSCs, but not the B220(+) counterparts. Compared with B220(−) PMN-MDSCs and B220(−) Mo-MDSCs, the Ly6G(+)Ly6C(−)CD11b(+)B220(+) and Ly6G(−)Ly6C(+)CD11b(+)B220(+) cells from tumor-bearing mice spleens exhibited a more mature phenotype without immunosuppressive activity. Additionally, IL-6 deficiency attenuated the tumor-induced accumulation of MDSCs, B220(−) MDSCs and B220(−) PMN-MDSCs but increased the percentages of Gr1(+)CD11b(+)B220(+), Ly6G(+)Ly6C(−)CD11b(+)B220(+), and Ly6G(−)Ly6C(+)CD11b(+)B220(+) cells, indicating the opposing roles of the IL-6 signaling pathway in the expansion of B220(−) MDSCs and their B220(+) counterparts. Taken together, our findings indicate that the B220(+) subset is a distinct subset of Gr1(+)CD11b(+) cells functionally different from the B220(−) subpopulation during tumorigenesis and induction of MDSCs to B220(+) cells may be helpful for cancer therapy.