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CD22

Official Full Name
CD22 molecule
Organism
Homo sapiens
GeneID
933
Background
Predicted to enable CD4 receptor binding activity; protein phosphatase binding activity; and sialic acid binding activity. Involved in B cell activation; negative regulation of B cell receptor signaling pathway; and regulation of endocytosis. Located in early endosome and recycling endosome. Implicated in diffuse large B-cell lymphoma. [provided by Alliance of Genome Resources, Feb 2025]
Synonyms
SIGLEC2; SIGLEC-2;
Bio Chemical Class
Immunoglobulin
Protein Sequence
MHLLGPWLLLLVLEYLAFSDSSKWVFEHPETLYAWEGACVWIPCTYRALDGDLESFILFHNPEYNKNTSKFDGTRLYESTKDGKVPSEQKRVQFLGDKNKNCTLSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVSERPFPPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGVPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQLQDADGKFLSNDTVQLNVKHTPKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEVFLQVQYAPEPSTVQILHSPAVEGSQVEFLCMSLANPLPTNYTWYHNGKEMQGRTEEKVHIPKILPWHAGTYSCVAENILGTGQRGPGAELDVQYPPKKVTTVIQNPMPIREGDTVTLSCNYNSSNPSVTRYEWKPHGAWEEPSLGVLKIQNVGWDNTTIACAACNSWCSWASPVALNVQYAPRDVRVRKIKPLSEIHSGNSVSLQCDFSSSHPKEVQFFWEKNGRLLGKESQLNFDSISPEDAGSYSCWVNNSIGQTASKAWTLEVLYAPRRLRVSMSPGDQVMEGKSATLTCESDANPPVSHYTWFDWNNQSLPYHSQKLRLEPVKVQHSGAYWCQGTNSVGKGRSPLSTLTVYYSPETIGRRVAVGLGSCLAILILAICGLKLQRRWKRTQSQQGLQENSSGQSFFVRNKKVRRAPLSEGPHSLGCYNPMMEDGISYTTLRFPEMNIPRTGDAESSEMQRPPPDCDDTVTYSALHKRQVGDYENVIPDFPEDEGIHYSELIQFGVGERPQAQENVDYVILKH
Open
Disease
Acute myeloid leukaemia, B-cell lymphoma, Diabetes mellitus, Diffuse large B-cell lymphoma, Follicular lymphoma, Leukaemia, Lupus erythematosus, Lyme borreliosis, Lymphoma, Malignant haematopoietic neoplasm, Mature B-cell leukaemia, Mature B-cell lymphoma, Multiple myeloma, Transplant rejection
Approved Drug
3 +
Clinical Trial Drug
38 +
Discontinued Drug
2 +

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Detailed Information

CD22, a member of the sialic acid-binding immunoglobulin-like lectins (Siglec) family, is a key regulator of B cell function within the immune system. Within the immunoglobulin superfamily, CD22 is crucial in controlling B cell receptor (BCR) signaling, hence preserving B cell homeostasis. Establishing the activation threshold of B cells, controlling immunological responses, and making sure B cells do not become too active—which may otherwise cause detrimental disorders like autoimmunity—all depend on this regulating role.

Role of CD22 in B Cell Signaling

One of the unique qualities of CD22 is its double function in the control of BCR signaling. Interacting with Src family tyrosine kinases helps to activate downstream signaling pathways, therefore functioning as a positive regulator. Using its immunoreceptor tyrosine-based inhibitory motifs (ITIMs), CD22 also acts as an inhibitory receptor. These patterns attract cytoplasmic phosphatases such as SHP-1 and SHP-2, which dephosphorylate signaling molecules and thus reduce BCR signaling, hence avoiding overstimulation of B cells. Correct immune function depends on this delicate balance between activation and inhibition.

Figure 1 illustrates the structure of CD22 and its role in down-regulating BCR signaling through interactions with sialic acids and recruitment of phosphatases following ITIM phosphorylation.Figure 1. Structure, interactions, and functions of human CD22. (Lanza F, et al., 2020)

With an affinity for alpha-2,6-linked sialic acid, CD22 binds especially to sialylated glycoproteins. One of the main ligands for CD22 is a glycoprotein produced in B cells, CD45. On the same cell surface, however, cis interactions with sialic acids may cover the binding site for CD22. This technique enables exact control of CD22's interaction with outside ligands during immune responses, hence regulating BCR signaling in many circumstances.

Early on in B cell development, CD22 expression starts in pro-B and pre-B cells first intracellularly. The internal compartment gives way to the cell surface when B cells develop in CD22 expression. Mature B cells have this surface expression most of which CD22 regulates BCR signaling.

CD22 as a Target in Hematologic Cancers

CD22 is expressed on the surface of malignant B cells in a variety of B cell-related cancers, making it a highly valuable therapeutic target. In acute lymphoblastic leukaemia (ALL), over 90% of B cells express CD22; this is also true of other cancers like hairy cell leukaemia (HCL) and non-Hodgkin lymphoma (NHL). With therapeutic drugs such antibody-drug conjugates (ADCs), monoclonal antibodies, and chimeric antigen receptor T-cell (CAR-T) treatments, the high expression of CD22 on these cancer cells allows specific targeting.

CD22 in Autoimmune Diseases

Beyond cancer, CD22 is involved in the onset of autoimmune illnesses like Sjögren's syndrome and systemic lupus erythematosus (SLE). Defects in CD22 expression or signaling under these circumstances might cause B cell tolerance to be lost, therefore producing damaging autoantibodies and persistent inflammation. Therapies aiming at CD22 seek to control B cell activity and bring immunological balance back in individuals with these autoimmune diseases.

CD22 in Transplant Rejection and Neurodegenerative Diseases

The potential influence of sCD22 in neurodegenerative disorders and transplant rejection has attracted interest. After organ transplantation, raised sCD22 levels may be a valuable indicator of immune activation during rejection episodes, therefore helping to monitor transplant patients. Additionally, sCD22 may be involved in the pathology of NPC and Alzheimer's disease, where it could influence immune responses within the central nervous system. Knowing how CD22 causes these disorders might offer therapeutic intervention avenues.

The potential influence of sCD22 in neurodegenerative disorders and transplant rejection has attracted interest. After organ transplantation, raised sCD22 levels may be a valuable indicator of immune activation during rejection episodes, therefore helping to monitor transplant patients. Furthermore implicated in the pathogenesis of NPC and Alzheimer's disease, sCD22 might affect central nervous system immune responses. Knowing how CD22 causes these disorders might offer therapeutic intervention avenues.

CD22-Targeted Therapies

As scientists find uses outside of cancer and autoimmune illnesses, the promise of CD22-targeted treatments keeps growing. Current studies investigate how neurodegenerative illnesses and transplant rejection could be treated using CD22-targeted therapies. CD22's capacity to control B cell signaling and its overexpression in disease conditions make it a desirable target for new treatment approaches.

References:

  1. Lanza F, Maffini E, Rondoni M, et al. CD22 Expression in B-Cell Acute Lymphoblastic Leukemia: Biological Significance and Implications for Inotuzumab Therapy in Adults. Cancers (Basel). 2020;12(2):303.
  2. Clark EA, Giltiay NV. CD22: A Regulator of Innate and Adaptive B Cell Responses and Autoimmunity. Front Immunol. 2018;9:2235. Published 2018 Sep 28.
  3. Liu T, Dai X, Xu Y, et al. CD22 is a potential target of CAR-NK cell therapy for esophageal squamous cell carcinoma. J Transl Med. 2023;21(1):710. Published 2023 Oct 10.
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