The CD22 gene encodes a 140 kDa type I transmembrane glycoprotein that serves as a critical member of the SIGLEC (sialic acid-binding immunoglobulin-like lectin) family. Gene expression is highly restricted to B-lymphocytes, with strong surface expression on mature B cells and high RNA levels in lymphoid tissues such as lymph nodes and spleen ^[1]. The encoded protein functions as a potent inhibitory co-receptor of the B-cell receptor (BCR); upon ligand binding, its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) are phosphorylated, recruiting phosphatases like SHP-1 to attenuate B-cell activation and maintain peripheral tolerance ^[2]. Beyond its regulatory role, CD22 facilitates cell-cell adhesion by recognizing α2,6-linked sialic acids. Due to its restricted expression pattern, CD22 is a major diagnostic marker and therapeutic target in various B-cell malignancies, including hairy cell leukemia, B-cell non-Hodgkin lymphoma, and acute lymphoblastic leukemia (ALL), and it has also been implicated in the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) ^[3].

The huCD22 mouse model was generated by replacing the murine Cd22 sequence from aa.22 through exon 9 with the homologous human CD22 region, all while retaining the mouse signal peptide to facilitate appropriate protein expression. This model is applicable to the study of various autoimmune diseases, including systemic lupus erythematosus (SLE), as well as cancers such as hairy cell leukemia, B-cell non-Hodgkin lymphoma, and acute lymphoblastic leukemia (ALL), and to the development of CD22-targeted therapeutics.