CD22

CD22 is a cell-surface receptor primarily expressed on mature B lymphocytes. It is a member of the Siglec (sialic acid-binding immunoglobulin-like lectin) family, also known as Siglec-2, and is encoded by the CD22 gene on chromosome 19q13.4. The protein consists of an extracellular region containing one N-terminal V-type Ig-like domain followed by several C2-type Ig-like domains, a single transmembrane segment, and a cytoplasmic tail that harbors two immunoreceptor tyrosine-based inhibitory motifs (ITIMs).

CD22 binds sialylated glycoprotein ligands, preferring alpha2-6 linked sialic acids on cell surface glycoconjugates. In B cells, CD22 functions as a negative regulator of B-cell receptor (BCR) signaling. Upon engagement and ITIM phosphorylation, CD22 recruits SHP-1 phosphatase, which dampens proximal signaling events in the BCR pathway and modulates B-cell activation, maturation, and tolerance. The receptor also undergoes endocytosis after ligand binding, enabling internalization of bound antibodies or other payloads, a property exploited for therapeutic delivery.

Expression of CD22 is restricted mainly to mature B cells (including follicular and marginal zone subsets) and is largely absent from T cells and most myeloid cells. Expression decreases as B cells differentiate toward plasma cells.

Clinically, CD22 serves as an diagnostic and therapeutic target in B-cell malignancies and some autoimmune conditions. Therapeutics include antibody-based and antibody–drug conjugate approaches, such as inotuzumab ozogamicin (CD22-targeted ADC) for relapsed/refractory B-ALL, moxetumomab pasudotox (CD22-targeted immunotoxin) for hairy cell leukemia, and epratuzumab (humanized anti-CD22) investigated in autoimmunity and lymphoma.