CD56 (NCAM)

CD56 is a cell adhesion molecule involved in cell-to-cell and cell-matrix interactions during development and differentiation. CD56 interacts with components of the extracellular matrix such as fibroblast growth factor receptors and N-cadherin. It also triggers signaling cascades involving FYN-focal adhesion kinase (FAK), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K).

During nervous system development, CD56 regulates neurogenesis, neurite outgrowth, axonal guidance, synapse formation and cell migration. In the hematopoietic system, CD56 is involved in the expansion of T lymphocytes, B lymphocytes and natural killer (NK) cells.^3,4 In humans, CD56 is a common phenotypic marker for NK cells.

Structure

The CD56 isoforms are heavily glycosylated proteins named by their molecular weights.5 The larger isoforms are transmembrane proteins while NCAM-120 has no intracellular residues.
 

• NCAM-180 has a large cytoplasmic domain.
• NCAM-140 has a short cytoplasmic tail.
• NCAM-120 is glycophosphatidylinositol (GPI)-linked to the cell membrane.
   

NCAM-120 is the predominant isoform in immune cells.⁶

CD56 in Diseases

CD56 can be used as a biomarker to detect malignant tumors in the nervous system (e.g., medulloblastoma and astrocytoma), malignant NK/T-cell lymphomas and neuroendocrine carcinoma.⁷ Due to its overexpression in several cancers, anti-CD56 antibody-drug conjugates, such as lorvotuzumab mertansine⁷ and promiximab-duocarmycin, have been developed.⁸ CD56 can also be a surrogate marker for other diseases such as COVID-19 and dementia associated with Alzheimer’s disease.⁹

Antigen Distribution

CD56 is expressed in brain, on CD16⁺ natural killer (NK) cells, T cell subsets and dendritic cells but not on myeloid cells, erythrocytes or B cells. CD56 expression on NK lymphocytes increases upon activation.⁷ CD56 expression on non-human primate lymphocytes is similar to that observed on human peripheral blood lymphocytes, with a subset of CD16⁺ cells co-expressing CD56.¹⁰ Clone MY31 is appropriate for detection of CD56 in non-human primates.

CD56 and CD16 expression can be used to characterize NK cell populations. CD16⁺CD56^dim NK cells make up 90% of peripheral blood NK cell populations that can migrate to sites of inflammation. They are characterized by their cytolytic activity, expressing high levels of granzymes, perforin and cytolytic granules but low levels of cytokines. Conversely, CD16-CD56^bright NK cells produce cytokines such as IFN-γ, TNF-α, GM-CSF, IL-10 and IL-13. They migrate to secondary lymphoid organs and have low cytotoxic properties.¹⁰

Demonstrated Applications of CD56 Detection

Our in-house clone R19-760 was developed to be compatible with select fixation and permeabilization buffers in flow cytometry applications. BD scientists incorporated R19-760 into a 16-color antibody panel to characterize subsets of cytotoxic T cells and NK cells. The cytolytic potential of these cell populations were analyzed through the detection of granzyme K, granzyme B and perforin.¹¹