Chronic stress is now recognized as a risk factor for disease development and/or exacerbation. It has been shown to affect negatively the immune system and notably the humoral immune response. Corticotropin-releasing hormone (CRH) is known to play a crucial role in stress response. CRH receptors are expressed on different immune cells such as granulocytes, monocytes and T cells. However, up to now, no CRH receptor has been described on B cells which are key players of the humoral immune response. In order to highlight new pathways by which stress may impact immunity, we investigated the role of CRH in B cells. Here we show that splenic B cells express the CRH receptor 2 (CRHR2), but not CRHR1. This receptor is functional since CRH treatment of B cells activates different signaling pathways (e.g. p38) and decreases B cell viability. Finally, we show that immunization of mice with two types of antigens induces a more intense CRHR staining in secondary lymphoid organs where B cells are known to respond to the antigen. Altogether our results demonstrate, for the first time, that CRH is able to modulate directly B cell activity through the presence of CRHR2.