CD79a is a protein located on the surface of B-cells, a type of immune cell responsible for producing antibodies. This protein is also identified as Ig-alpha. Its main function involves assisting the B-cell in receiving and responding to signals from its surroundings, which is a fundamental aspect of immune system communication.
The Role of CD79a in B-Cell Function
CD79a does not operate independently; it forms a heterodimer with another protein, CD79b, through a disulfide bond. Together, this CD79a/CD79b dimer associates non-covalently with membrane-bound immunoglobulin molecules to form the B-cell receptor (BCR) complex. The BCR functions like an antenna, scanning for antigens. When the BCR encounters and binds to an antigen, CD79a and CD79b act as internal signaling components, transmitting a “go” command into the B-cell.
This signal initiation involves the phosphorylation of tyrosine residues within the cytoplasmic domains of CD79a and CD79b by enzymes called Src-family kinases. These phosphorylated sites, known as immunoreceptor tyrosine-based activation motifs (ITAMs), then recruit other signaling molecules, such as Syk kinase. This recruitment triggers a cascade of downstream events, including the activation of pathways like PI3K, NF-κB, and MAPK, which amplify the antigen recognition signal. This signaling pathway ultimately leads to the activation of the mature B-cell, prompting it to proliferate and differentiate into antibody-producing plasma cells, which are important for fighting infections.
Importance in B-Cell Development
CD79a holds a role in the early stages of B-cell formation, separate from its function in mature cells. B-cells originate and undergo a selection process within the bone marrow. CD79a, in conjunction with CD79b, is a component of the pre-B-cell receptor (pre-BCR), which is expressed transiently on developing B-cells. This pre-BCR complex includes a rearranged mu heavy chain and a surrogate light chain, alongside the CD79a/CD79b signaling module.
The association of CD79a/CD79b with the immunoglobulin heavy chain is necessary for the surface expression of the pre-BCR. This expression provides survival signals that inform the developing B-cell it has successfully assembled its initial receptor components. Without these signals, the developing B-cell would fail this quality control checkpoint and be eliminated, preventing the release of improperly formed B-cells into the body. Mutations or genetic deletions affecting CD79a can therefore block B-cell development at the pro-B to pre-B cell transition stage.
CD79a in Disease and Diagnosis
Alterations in the CD79a gene can lead to health issues, particularly affecting the immune system. When the CD79a gene is mutated or absent, individuals may develop a primary immunodeficiency, a form of agammaglobulinemia. This condition is characterized by an inability to produce mature B-cells and antibodies, leading to a lack of effective humoral immune response. Early diagnosis and immunoglobulin replacement therapy are important for managing the disease.
Beyond inherited disorders, CD79a serves as a marker in the diagnosis of certain cancers. Because CD79a is consistently present on B-cells, it is used in laboratory tests, such as immunohistochemistry, to identify cancers originating from B-cells. Its presence helps confirm the B-cell lineage of malignant cells in various lymphomas and leukemias, including diffuse large B-cell lymphoma and B-cell lymphoblastic leukemia. This expression makes CD79a an indicator for classifying these types of blood cancers, guiding treatment strategies.
Therapeutic Targeting of CD79a
CD79a’s presence on the surface of B-cells, including cancerous ones, makes it a target for certain cancer therapies. An approach involves antibody-drug conjugates (ADCs), which act like guided missiles to deliver chemotherapy to cancer cells. An ADC consists of an antibody, which serves as the guidance system, linked to a chemotherapy drug, the “warhead”. The antibody component is designed to recognize and bind to a protein like CD79a or its partner CD79b on the surface of cancer cells.
Once the antibody binds to the target protein, the complex is internalized by the cell. Inside the cancer cell, the linker connecting the antibody and the drug is cleaved, releasing the chemotherapy agent into the cell’s cytoplasm. This targeted delivery minimizes the exposure of healthy tissues to chemotherapy, reducing systemic side effects. For example, Polatuzumab vedotin is an ADC that targets CD79b, and has shown efficacy in treating B-cell non-Hodgkin lymphoma by delivering a microtubule-disrupting agent to malignant B-cells.