B-cell receptor

The B-cell receptor or BCR is a transmembrane receptor protein located on the outer surface of B cells. The receptor's binding moiety is composed of a membrane-bound antibody that, like all antibodies, has a unique and randomly determined antigen-binding site (see V(D)J recombination). When a B cell is activated by its first encounter with an antigen that binds to its receptor (its "cognate antigen"), the cell proliferates and differentiates to generate a population of antibody-secreting plasma B cells and memory B cells. The B cell receptor (BCR) has two crucial functions upon interaction with the antigen. One function is signal transduction, involving changes in receptor oligomerization. The second function is to mediate internalization for subsequent processing of the antigen and presentation of peptides to helper T cells. BCR functions are required for normal antibody production, and defects in BCR signal transduction may lead to immunodeficency, and B-cell malignancy.

The B-cell receptor is composed of two parts: i) A membrane-bound immunoglobulin molecule of one isotype (IgD, IgM, IgA, IgG, or IgE). With the exception of the presence of an integral membrane domain, these are identical to their secreted forms. ii) 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).

There are several signaling pathways that the B-cell receptor can follow through. The physiology of B cells is intimately connected with the function of their B-cell receptor. In B cells, the balance of initiation, amplitude and duration of BCR activation can be influenced by a specific immunoglobulin structure, the expression adaptor molecules (like GAB1, BLNK, GRB2, CARD11), the activity of kinases (like LYN, SYK, PI3K) or phosphatases (like SHIP-1, SHP-1 and PTEN) and levels of microRNAs. The miR-150 and miR-155 were shown to be regulators of proteins that affect the propensity of BCR signalling pathway.

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