CD79A molecule | Elisa - Clia - Antibody - Protein

Background

CD79A, also known as Ig-alpha, is a protein encoded by the CD79A gene in humans. It is a crucial component of the B cell receptor (BCR) complex, playing a significant role in B cell development, activation, and signaling. The BCR complex is essential for the adaptive immune response, allowing B cells to recognize and respond to specific antigens. CD79A, along with CD79B (Ig-beta), forms the signaling component of the BCR, transmitting signals from the antigen-bound surface immunoglobulin (Ig) to the cell's interior, initiating a cascade of intracellular events leading to B cell activation, proliferation, and differentiation.

Protein Structure

CD79A is a transmembrane protein comprising 226 amino acids. It has several distinct structural features:

• Extracellular Domain: The N-terminal extracellular region of CD79A contains an immunoglobulin-like domain responsible for interactions with the surface immunoglobulin molecule. This region also contains glycosylation sites essential for protein stability and function.
• Transmembrane Domain: The transmembrane region anchors CD79A in the cell membrane and is involved in interactions with CD79B, forming a stable complex that associates with surface immunoglobulins.
• Intracellular Domain: The intracellular C-terminal region contains immunoreceptor tyrosine-based activation motifs (ITAMs), which are crucial for signal transduction. Upon antigen binding to the BCR, the ITAMs are phosphorylated by Src-family kinases, initiating downstream signaling pathways that lead to B cell activation.

Classification and Subtypes

CD79A is classified as a member of the immunoglobulin superfamily and is one of the two components of the BCR complex, the other being CD79B. There are no known subtypes of CD79A, but it works in conjunction with CD79B to perform its functions within the BCR complex.

Function and Biological Significance

B Cell Development:

• CD79A is essential for early B cell development in the bone marrow. It forms a complex with CD79B and associates with the pre-B cell receptor (pre-BCR) during the early stages of B cell maturation. Signaling through the pre-BCR is critical for the selection and expansion of pre-B cells, ensuring the proper development of functional B cells.

Antigen Recognition and Signal Transduction:

• The primary function of CD79A is to transmit signals from the surface immunoglobulin to the interior of the B cell upon antigen binding. This signaling is initiated by the phosphorylation of ITAMs in the intracellular domain of CD79A, leading to the activation of downstream signaling pathways, including the MAPK, PI3K, and NF-κB pathways.

B Cell Activation and Proliferation:

• CD79A-mediated signaling is crucial for B cell activation, proliferation, and differentiation. Upon antigen binding, the BCR complex, including CD79A, initiates signaling cascades that result in the activation of transcription factors, cytokine production, and the clonal expansion of B cells. This process is vital for the generation of an effective immune response.

Role in Immune Responses:

• CD79A, as part of the BCR complex, is involved in both T cell-dependent and T cell-independent immune responses. In T cell-dependent responses, CD79A signaling helps in the formation of germinal centers, where B cells undergo somatic hypermutation and class-switch recombination, leading to the production of high-affinity antibodies. In T cell-independent responses, CD79A signaling can directly activate B cells in response to certain antigens, such as polysaccharides.

Clinical Issues

Immunodeficiencies:

• Mutations or deficiencies in CD79A can lead to primary immunodeficiencies, characterized by impaired B cell development and function. Patients with CD79A deficiencies may present with hypogammaglobulinemia, recurrent infections, and an inability to mount effective antibody responses.

Autoimmune Diseases:

• Dysregulation of CD79A signaling has been implicated in autoimmune diseases. Aberrant activation of B cells through the BCR complex can contribute to the production of autoantibodies, leading to conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Lymphomas and Leukemias:

• CD79A is expressed in various B cell malignancies, including B cell lymphomas and leukemias. The expression of CD79A is often used as a diagnostic marker in the immunophenotyping of these malignancies. Moreover, CD79A signaling pathways are potential therapeutic targets in the treatment of B cell cancers.

Therapeutic Targeting:

• CD79A has emerged as a target for novel therapeutic strategies. Antibody-drug conjugates (ADCs) targeting CD79A, such as polatuzumab vedotin, have shown promising results in the treatment of B cell lymphomas. These therapies aim to deliver cytotoxic agents directly to malignant B cells, minimizing damage to healthy tissues.

Summary

CD79A is a critical component of the B cell receptor complex, essential for B cell development, activation, and signaling. Its structure comprises an extracellular domain for antigen binding, a transmembrane domain for complex formation, and an intracellular domain with ITAMs for signal transduction. CD79A plays a pivotal role in immune responses, both T cell-dependent and T cell-independent, and is implicated in various clinical conditions, including immunodeficiencies, autoimmune diseases, and B cell malignancies. Understanding the molecular mechanisms of CD79A and its role in B cell biology provides valuable insights for the development of targeted therapies for these conditions.