CD4⁺ T Cell‐Released Extracellular Vesicles Potentiate the Efficacy of the HBsAg Vaccine by Enhancing B Cell Responses

T cells secrete bioactive extracellular vesicles (EVs), but the potential biological effects of CD4⁺ T cell EVs are not clear. The main purpose of this study is to investigate the effects of CD4⁺ T cell-derived EVs on B cell responses and examine their role in antigen-mediated humoral immune responses. In this study, CD4⁺ T cell EVs are purified from activated CD4⁺ T cells in vitro. After immunization with the Hepatitis B surface antigen (HBsAg) vaccine, CD4⁺ T cell EVs-treated mice show stronger humoral immune responses, which is indicated by a greater Hepatitis B surface antibody (HBsAb) level in serum and a greater proportion of plasma cells in bone marrow. In addition, it is found that EVs released from activated CD4⁺ T cells play an important role in B cell responses in vitro, which significantly promote B cell activation, proliferation, and antibody production. Interestingly, antigen-specific CD4⁺ T cell EVs are found to be more efficient than control EVs in enhancing B cell responses. Furthermore, it is shown that CD40 ligand (CD40L) is involved in CD4⁺ T cell EVs-mediated B cell responses. Overall, the results have demonstrated that CD4⁺ T cell EVs enhance B cell responses and serve as a novel immunomodulator to promote antigen-specific humoral immune responses.