Question

7. Describe the structure of the B-cell receptor (BCR). How is the BCR able to trigger a signal transduction pathway when its cytoplasmic tail is only 3 amino acids in length? Outline BCR signal transduction from the point of antigen binding through the NF-κB pathway. What is the result of signal transduction events from the BCR?

Answer 1

7) The B-cell receptor(BCR):

Structure of BCR:

B-cell receptor is a transmembrane receptor protein located on the outer surface of B cells. The receptor's binding moietyis composed of a membrane-bound antibody that, like all antibodies, has a unique and randomly determined antigen-binding site.It has two components,namely;

• A membrane-bound immunoglobulin molecule of one isotype (IgD, IgM, IgA, IgG, or IgE)
• Signal transduction moiety: A heterodimer called Ig-α/Ig-β (CD79), bound together by disulfide bridges. Each member of the dimer spans the plasma membrane and has a cytoplasmic tail bearing an immunoreceptor tyrosine-based activation motif (ITAM).

BCR signal transduction pathway:

• All isotypes of mIg have very short cytoplasmic tails. Both mIgM and mIgD have a cytoplasmic domain, which are only 3 amino acids in length.
• The cytoplasmic tails of mIg are too short to be able to associate with intracellular signaling molecules.
• Since mIg is always associated with the Ig-α/Ig-β heterodimer collectively forming B-Cell receptor complex (BCR), two molecules of this heterodimer associate with one mIg to form a single BCR.
• The Ig-α/Ig-β heterodimer carries out the signal transducing function of the complex.The Ig-α chain has a long cytoplasmic domain containing 61 amino acids while the Ig-β chain has a long cytoplasmic domain containing 48 amino acids.

BCR signal transduction from the point of antigen binding through the NF-κB pathway:

NF-κB plays the most important role is the immune system.NF-κB regulates the expression of cytokines, growth factors, and effector enzymes in response to ligation of many receptors involved in immunity including T-cell receptors (TCRs) and B-cell receptors (BCRs).Signaling from BCRs is critical for mounting adaptive immune responses and has consequently been of great interest. Activation of NF-κB downstream of BCR allows antigen-specific proliferation and maturation of lymphocytes into effector cells. Signaling through these two antigen receptors is functionally analogous, although the molecular details differ.