CD200 is a transmembrane glycoprotein belonging to the immunoglobulin superfamily that plays crucial roles in various biological processes. CD200 is expressed on a wide range of cell types, including B cells, certain subsets of T cells (including activated T cells), thymocytes, endothelial cells, and neurons. In normal B cells, CD200 is moderately expressed on peripheral blood B cells, bone marrow B-cell precursors, and reactive lymph node CD10-negative follicular extrafollicular center (EFC) B cells. It is weakly expressed on reactive lymph node CD10-positive follicular center (FC) B cells. In B-cell malignancies, the expression of CD200 is heterogeneous. For instance, it is highly expressed in hairy cell leukemia (HCL) and moderately to highly expressed in chronic lymphocytic leukemia (CLL) and Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (LPL). However, the expression in large B-cell lymphomas (LBCL), follicular lymphomas (FL), and marginal zone lymphomas (MZL) varies significantly. CD200 produces immunosuppressive signals through binding to its cognate receptor, CD200 receptor 1 (CD200R1), which is expressed on granulocytes, monocytes, and subsets of T cells. This interaction plays a significant role in immune regulation. Studies have shown that CD200, acting through its receptor CD200R1, can inhibit excessive microglial activation induced by chronic stress, alleviate damage to adult hippocampal neurogenesis, and improve depressive-like behavior in mice, revealing a new mechanism of neuron-glial cell interaction in the occurrence of depression.