Other - B cells , immunology
B cells secreting granzyme B (GZMB+) with suppressive properties have been evidenced in a growing number of immunological contexts, autoimmunity, chronic infection, neoplasias as well as in healthy volunteers in physiological conditions. Until now, no phenotype has been proposed for these GZMB+ B cells and their biology as well is still not understood. We found that GZMB+ B cells are mature IgD low/- B cells harboring a CD19int BACE2int CD266lo LAG3int CD307blo enriched profile. We demonstrate our ability to expand these GZMB+ B cells that express high level of regulatory molecules after expansion and still display suppressive functions, blocking CD4+CD25- effector T cells proliferation in a GZMB dependent manner, whereas keeping their ability to differentiate, activate and produce immunoglobulins. Accordingly to their BCR usage, we show that GZMB+ and GZMB- B cells likely share a common B cell progenitor. Finally, we report that GZMB+ B cells expand under the control of GZMB through phosphorylation of ERK1/2 whereas they are more prone to apoptosis compared with their GZMB- B cell counterpart, suggesting their endocrinous tight control. These data bring new insights into the GZMB+ B cell biology and function that emerge as one component of a complex regulatory network. Success to expand them while keeping their potent immunosuppressive properties provides new clues for novel future cell therapies.