CD45 positive cells carry the Cluster of Differentiation 45 (CD45) protein marker on their surface. This surface marker serves as a universal identification tag for almost every cell belonging to the body’s blood-forming and immune system, collectively called hematopoietic cells. Identifying a cell as “CD45 positive” immediately places it within the immune system, making this marker a foundational concept in immunology. The presence of CD45 is widespread, making its detection a primary step in clinical diagnostics.
Understanding the CD45 Protein Marker
The CD45 protein is a large, complex molecule embedded within the outer membrane of a cell. Historically known as the Leukocyte Common Antigen (LCA), it is ubiquitous across white blood cells, or leukocytes. As a transmembrane protein, CD45 spans the entire width of the cell membrane, featuring an external portion, a membrane-crossing segment, and a part that extends into the cell’s interior.
The physical location of this protein on the cell surface means it is perfectly positioned to interact with the external environment while also transmitting signals into the cell’s machinery. Its presence is the defining feature that allows scientists and clinicians to distinguish immune cells from non-immune cells, such as epithelial cells, muscle cells, or mature red blood cells, which are all considered “CD45 negative.” The molecule’s structure is also subject to variation, with different versions, or isoforms, expressed depending on the specific type and maturation stage of the immune cell.
These different isoforms arise from a process called alternative splicing, where specific gene segments are included or excluded during the protein’s production. For instance, a naïve T cell that has not yet encountered an antigen may express a different, longer isoform than a memory T cell that is primed for a rapid immune response. This ability to express various forms allows the CD45 marker to encode information about the cell’s history and functional readiness.
The Role of CD45 in Immune Cell Signaling
Beyond its function as an identifier, CD45 is a highly active enzyme known specifically as a protein tyrosine phosphatase (PTP). This enzymatic function makes the protein a central regulator of immune cell activity, acting like a molecular switch. It performs its regulation by removing phosphate groups from other signaling proteins within the cell, a process called dephosphorylation.
This dephosphorylation is particularly important in controlling the activity of Src family kinases, such as Lck and Fyn, which are proteins that promote cell activation. In T cells, CD45 dephosphorylates an inhibitory site on Lck, effectively activating the kinase and preparing the T cell to respond to an antigen. This action is necessary for the T cell receptor (TCR) to successfully transmit a signal that initiates an immune response.
Conversely, in some contexts, CD45 can also act to dampen or fine-tune the immune response by regulating the phosphorylation status of other molecules. Its dual ability to both promote and inhibit signaling pathways means that CD45 sets the activation threshold for immune cells, determining how sensitive they are to external stimuli. Without CD45, T cells and B cells cannot properly respond to antigens, demonstrating the protein’s necessity in the coordinated initiation and cessation of the body’s defense mechanisms.
The Diversity of Cells Expressing CD45
The CD45 protein is expressed by the entire family of nucleated hematopoietic cells, encompassing all major branches of the immune system. These cells are broadly categorized into lymphocytes, myeloid cells, and dendritic cells, each playing distinct roles in defending the body.
Lymphocytes, responsible for adaptive immunity, include T cells, B cells, and Natural Killer (NK) cells. T cells coordinate targeted responses against pathogens. B cells produce antibodies that neutralize foreign invaders, and NK cells patrol the body to destroy infected or cancerous cells directly.
Myeloid cells form the core of the innate immune system. This category includes monocytes, which mature into macrophages in tissues to engulf cellular debris and pathogens. Neutrophils, the most abundant white blood cell, are rapid responders that primarily kill bacteria through phagocytosis and the release of toxic substances.
Dendritic cells, another type of myeloid cell, act as professional antigen-presenting cells that capture foreign material and present it to T cells to initiate a full adaptive immune response. While all these cell types express CD45, the intensity of expression can vary significantly; for instance, lymphocytes typically exhibit the brightest CD45 signal compared to other leukocytes. This variation in expression intensity, along with the specific isoforms present, reflects the cell’s distinct function and developmental stage.
CD45 Detection in Health and Disease Diagnosis
The universal presence of CD45 on all white blood cells makes its detection an indispensable tool in clinical and diagnostic settings. The primary method for utilizing CD45 is flow cytometry, where cells from a sample are labeled with fluorescent antibodies that specifically bind to the CD45 protein.
CD45 serves as a “gating marker,” a parameter used to draw a boundary on a plot to isolate the entire population of white blood cells for further analysis. By gating on the CD45-positive cells, clinicians can accurately separate the immune cells from all other components in the sample, such as debris or non-immune cells. This initial step is fundamental for quantifying the total number of immune cells and then identifying specific subsets, such as T cells or B cells, using additional markers.
CD45 status is particularly important in diagnosing and classifying hematologic malignancies, including leukemias and lymphomas. The expression pattern of CD45 helps to distinguish cancerous immune cells from normal ones, and the intensity of the CD45 signal can provide clues about the cell’s maturity. For instance, a low or absent CD45 expression can be a feature used to identify some acute leukemias and plasma cell neoplasms. The CD45 marker is a precise diagnostic tool that helps to pinpoint the type and stage of a disease.

