B-cell receptor CD22 (CD22) (CD22)

B-cell receptor CD22, also known as Siglec-2, is a 140 kDa type I transmembrane sialoglycoprotein and a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family [1, 4]. It is expressed specifically on the surface of mature B cells and serves as a critical inhibitory co-receptor that regulates B-cell receptor (BCR) signaling [1, 10]. Upon BCR activation, CD22 is phosphorylated on its immunoreceptor tyrosine-based inhibitory motifs (ITIMs), leading to the recruitment of the phosphatase SHP-1, which dampens downstream signaling to maintain immune homeostasis and self-tolerance [1, 14]. In B-cell malignancies such as acute lymphoblastic leukemia (B-ALL) and various lymphomas, CD22 is frequently overexpressed, making it a prominent therapeutic target [11, 15]. Clinical interventions include antibody-drug conjugates (ADCs) like inotuzumab ozogamicin, which utilize the rapid internalization of CD22 to deliver cytotoxic payloads, and CAR-T cell therapies designed to eliminate malignant B cells [10, 16]. Despite its efficacy, therapeutic challenges include the risk of antigen loss or downregulation leading to disease relapse, as well as safety concerns such as cytokine release syndrome and hepatotoxicity [15, 16].

Other names

Siglec-2Sialic acid-binding Ig-like lectin 2B-lymphocyte cell adhesion moleculeBL-CAMT-cell surface antigen Leu-14

CD22 functions as an inhibitory co-receptor that recruits protein tyrosine phosphatase SHP-1 to dephosphorylate signaling molecules in the B-cell receptor (BCR) complex, thereby suppressing B-cell activation [1, 4, 14]. Therapeutic agents target CD22 to deliver cytotoxic payloads via internalization (ADCs and immunotoxins) or to direct T-cell mediated lysis (CAR-T cells) [10, 11, 15, 16].