The CD45 marker is a large protein found on the surface of nearly all cells originating from the hematopoietic system, which includes blood-forming cells in the bone marrow. This protein is widely recognized as the Leukocyte Common Antigen (LCA) because of its broad presence across various types of white blood cells, also known as leukocytes. Its consistent expression on these cells makes CD45 a fundamental tool for distinguishing immune cells from other cell types found in the body, such as epithelial cells, muscle cells, or nerve cells. This identification capability forms the basis for understanding immune cell populations and their roles in health and disease.
The Core Function of CD45 in the Immune System
CD45 operates as a protein tyrosine phosphatase (PTP), which means it removes phosphate groups from specific tyrosine amino acids on other proteins. This action functions like a molecular switch, carefully regulating internal signaling pathways within immune cells. By controlling the phosphorylation state of various proteins, CD45 influences how immune cells interpret and respond to external cues. This precise regulation is important for maintaining immune system balance.
The protein’s official name, Protein Tyrosine Phosphatase Receptor Type C (PTPRC), highlights its nature as a receptor-like enzyme. CD45 plays an important role in the activation of both T-cells and B-cells, two types of lymphocytes that are central to adaptive immunity. For instance, in T-cells, CD45 modulates the activity of kinases like Lck and Fyn, which are enzymes involved in transmitting signals from the T-cell receptor. Proper CD45 activity is needed for these T-cells to become activated and carry out their functions, such as recognizing and eliminating infected cells.
Similarly, in B-cells, CD45 influences signaling pathways initiated by the B-cell receptor, affecting processes like B-cell development and antibody production. Its phosphatase activity helps fine-tune the sensitivity of these cells to antigen stimulation, ensuring an appropriate immune response.
Identifying Immune Cells with CD45 Isoforms
The CD45 protein can exist in multiple distinct forms known as isoforms. These variations arise from a biological process called alternative splicing, where different segments of the CD45 gene’s messenger RNA are included or excluded during protein synthesis. The presence of specific isoforms on the cell surface allows scientists to differentiate between various functional states and developmental stages of immune cells.
Among the most recognized isoforms are CD45RA and CD45RO, which serve as markers for distinct populations of T-cells. CD45RA is typically expressed on naive T-cells, which have not yet encountered their specific antigen.
Conversely, CD45RO is generally found on memory T-cells, which have previously been activated by an antigen and have differentiated to provide a quicker and stronger response upon subsequent exposure to the same antigen. T-cells transition from expressing CD45RA to CD45RO after they are activated, reflecting their shift from a naive to an experienced state. This distinct expression pattern allows researchers and clinicians to distinguish between naive and memory T-cell populations, providing insights into an individual’s immune history.
The Role of CD45 in Medical Diagnostics and Research
The presence or absence of the CD45 marker, along with its specific isoforms, serves as an important diagnostic tool in medical settings. Techniques like flow cytometry and immunohistochemistry (IHC) frequently utilize antibodies that bind to CD45 to identify and quantify immune cells. In flow cytometry, cells are passed through a laser beam, and fluorescently tagged antibodies against CD45 allow for the rapid identification and counting of leukocyte populations in a fluid sample. Immunohistochemistry involves applying CD45 antibodies to tissue sections, with positive cells showing a color change under a microscope, helping pathologists visualize immune cells within tissues. Beyond diagnostics, CD45 is also used in research to isolate specific immune cell populations, allowing scientists to study their functions in detail and understand their roles in various diseases.
An important application of CD45 in pathology is its ability to differentiate between various types of cancer, particularly those originating from blood-forming cells versus other tissues. Lymphomas and leukemias, cancers of lymphocytes and other hematopoietic cells, almost universally express CD45 and are therefore considered CD45-positive. Most malignant lymphomas are CD45 positive.
In stark contrast, carcinomas, which are cancers arising from epithelial cells (like lung, breast, or colon cancer), do not express CD45 and are thus CD45-negative. This clear distinction is important for pathologists when diagnosing undifferentiated tumors, aiding in accurate classification and guiding appropriate treatment strategies. Therapies for lymphomas and leukemias differ substantially from those for carcinomas.