PAX5

The Pathology Dictionary Team
May 21, 2023

What is PAX5?

PAX5 (Paired box protein 5) is a type of protein called a transcription factor that plays an important role in the development and function of B cells, a type of white blood cells (WBCs) that are part of the body’s immune system. It is also known as BSAP (B-cell-specific activator protein) due to its specific expression in B cells.

What does PAX5 do?

PAX5 plays an important role in the development and normal function of B cells.

PAX5 contributes to the following functions:

• Transcriptional regulation: PAX5 functions as a transcription factor, meaning it binds to specific parts of the cell’s DNA and controls the expression of genes involved in B cell development and maturation. It acts as a master regulator of B cell lineage commitment and differentiation.
• B cell development: PAX5 is crucial for the early stages of B cell development in the bone marrow. It helps establish the B cell lineage by promoting the expression of genes associated with B cell identity and repressing genes that would lead to the development of other cell types.
• Immunoglobulin production: PAX5 regulates the expression of genes encoding immunoglobulins (antibodies) in mature B cells. It ensures that B cells produce functional and diverse antibodies that can recognize a wide range of pathogens.
• Maintenance of B cell identity: PAX5 is involved in maintaining the identity and function of mature B cells. It helps suppress the expression of genes associated with other cell types and reinforces the B cell-specific gene expression program.
• Tumor suppressor role: PAX5 acts as a tumour suppressor in B cell lymphomas, a type of cancer that originates from B cells. Loss or inactivation of PAX5 can contribute to the development of lymphomas.

What types of cells normally express PAX5?

PAX5 is primarily expressed in B cells, a type of white blood cells (WBCs) that are part of the body’s immune system. B cells are responsible for producing specialized immune proteins called immunoglobulins (antibodies) and play a crucial role in the adaptive immune system.

PAX5 is expressed throughout the development of normal B cells including:

• Pro-B cells: PAX5 is first expressed in the early stages of B cell development, specifically in pro-B cells. Pro-B cells are the earliest committed B cell precursors found in the bone marrow. PAX5 is critical for initiating the commitment to B cell lineage and driving the expression of genes associated with B cell development.
• Pre-B cells: PAX5 continues to be expressed as B cells progress to the pre-B cell stage. Pre-B cells are characterized by the rearrangement and expression of the immunoglobulin heavy chain genes. PAX5 plays a role in regulating this rearrangement process and the subsequent maturation of pre-B cells.
• Mature B cells: PAX5 expression persists in mature B cells, which are found in secondary lymphoid organs such as the spleen and lymph nodes. In mature B cells, PAX5 maintains the B cell identity by regulating the expression of genes associated with B cell function, including immunoglobulin genes.

While PAX5 is predominantly expressed in B cells, it can also be detected at lower levels in other cell types, such as certain subsets of T cells, plasma cells, and some non-lymphoid cells. However, its expression in these cells is usually limited or transient compared to its robust and specific expression in B cells.

What types of tumours express PAX5?

PAX5 is expressed by tumours made up of B cells. These types of tumours are called lymphomas.

B cell lymphomas that commonly express PAX5 include:

• Diffuse large B cell lymphoma (DLBCL): DLBCL is the most common type of non-Hodgkin lymphoma. PAX5 is frequently expressed in DLBCL, indicating its B cell origin.
• Burkitt lymphoma: Burkitt lymphoma is an aggressive form of B cell lymphoma. PAX5 is typically expressed in Burkitt lymphoma cells and is considered a diagnostic marker for this type of lymphoma.
• B cell lymphoblastic lymphoma/leukemia: This is a type of lymphoma/leukemia that arises from immature B cells. PAX5 expression is commonly observed in B cell lymphoblastic lymphoma/leukemia and can aid in its diagnosis.
• Mantle cell lymphoma: Mantle cell lymphoma is characterized by the overexpression of cyclin D1, but PAX5 is still expressed in the tumour cells, reflecting their B cell origin.
• Follicular lymphoma: Follicular lymphoma is a slow-growing B cell lymphoma. While PAX5 expression may be diminished compared to normal B cells in some cases, it is still often detected in follicular lymphoma.

It’s important to note that PAX5 expression alone is not sufficient for diagnosing these lymphomas, and other markers and tests are usually required for accurate classification. Nonetheless, the presence of PAX5 in tumour cells can provide valuable information about their B cell lineage and help guide diagnosis and treatment decisions.