Abstract T cell/B cell mixed phenotypic lymphocytes have been observed in different disease contexts, yet their presence and function in physiological conditions remain elusive. Here, we provide evidence for the existence of a lymphocyte subset endogenously expressing both T- and B-cell lineage markers in mice. The majority of these T/B phenotypic lymphocytes (CD3+CD19+) show an origin of pro/pre B cells and distribute widely in mouse bone marrow, lymph nodes, spleen, and peripheral blood. Functional assays show that these biphenotypic lymphocytes can be activated through stimulating TCR or BCR signaling pathways. Moreover, we show that these cells actively participate both the humoral and cellular immune responses elicited by vaccination. Compared to conventional T cells, these biphenotypic lymphocytes can secrete a higher level of IL-2 but a lower level of TNF-α upon antigen specific stimulation. An equivalent lymphocyte subset is found in freshly isolated human PBMCs and exhibits similar functionality, albeit at a lower frequency than in mice.
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