B-cell receptor

The B cell receptor (BCR) is a transmembrane protein on the surface of a B cell. B cell receptors are composed of immunoglobulin molecules that form a type 1 transmembrane receptor protein, and are typically located on the outer surface of these lymphocyte cells. Through biochemical signaling and by physically acquiring antigens from the immune synapses, the BCR controls the activation of the B cell. B cells are able to gather and grab antigens by engaging biochemical modules for receptor clustering, cell spreading, generation of pulling forces, and receptor transport, which eventually culminates in endocytosis and antigen presentation. B cells' mechanical activity adheres to a pattern of negative and positive feedbacks that regulate the quantity of removed antigen by manipulating the dynamic of BCR–antigen bonds directly. Particularly, grouping and spreading increase the relation of antigen with BCR, thereby proving sensitivity and amplification. On the other hand, pulling forces delinks the antigen from the BCR, thus testing the quality of antigen binding.
The receptor's binding moiety is composed of a membrane-bound antibody that, like all antibodies, has two identical paratopes that are unique and randomly determined. The BCR for an antigen is a significant sensor that is required for B cell activation, survival, and development. 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.
Development and structure of the B cell receptor.
The first checkpoint in the development of a B cell is the production of a functional pre-BCR, which is composed of two surrogate light chains and two immunoglobulin heavy chains, which are normally linked to Ig-α and Ig-β signaling molecules. Each B cell, produced in the bone marrow, is highly specific to an antigen. The BCR can be found in a number of identical copies of membrane proteins that are exposed at the cell surface.
The B cell receptor is composed of two parts:
More analytically, the BCR complex consists of an antigen-binding subunit known as the membrane immunoglobulin (mIg), which is composed of two immunoglobulin light chains (IgLs) and two immunoglobulin heavy chains (IgHs) as well as two heterodimer subunits of Ig-α and Ig-β. In order for mIgM molecules to transport to the surface of the cell, there must be a combination of Ig-α and Ig-β with the mIgM molecules. Pre-B cells that do not generate any Ig molecule normally carry both Ig-α and Ig-β to the cell surface.
Heterodimers may exist in the B cells as either an association or combination with another pre B cell-specific proteins or alone, thereby replacing the mIgM molecule. Within the BCR, the part that recognizes antigens is composed of three distinct genetic regions, referred to as V, D, and J. All these regions are recombined and spliced at the genetic level in a combinatorial process that is exceptional to the immune system. There are a number of genes that encode each of these regions in the genome and can be joined in various ways to generate a wide range of receptor molecules. The production of this variety is crucial since the body may encounter many more antigens than the available genes. Through this process, the body finds a way of producing multiple different combinations of antigen-recognizing receptor molecules. Heavy chain rearrangement of the BCR entails the initial steps in the development of B cell. The short JH (joining) and DH (diversity) regions are recombined first in early pro-B cells in a process that is dependent on the enzymes RAG2 and RAG1. After the recombination of the D and J regions, the cell is now referred to as a “late pro-B” cell and the short DJ region can now be recombined with a longer segment of the VH gene.
BCRs have distinctive binding sites that rely on the complementarity of the surface of the epitope and the surface of the receptor, which often occurs by non-covalent forces. Mature B cells can only survive in the peripheral circulation for a limited time in when there is no specific antigen. This is because when cells do not meet any antigen within this time, they will go through apoptosis. It is notable that in the peripheral circulation, apoptosis is important in maintaining an optimal circulation of B-lymphocytes. In structure, the BCR for antigens are almost identical to secreted antibodies. However, there is a distinctive structural dissimilarity in the C-terminal area of the heavy chains, as it consists of a hydrophobic stretch that is short, which spreads across the lipid bilayer of the membrane.
Signaling pathways of the B cell receptor.
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. The BCR signaling pathway is initiated when the mIg subunits of the BCR bind a specific antigen. The initial triggering of the B cell receptor is similar for all receptors of the non-catalytic tyrosine-phosphorylated receptor family. The binding event allows phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the associated Igα/Igβ heterodimer subunits by the tyrosine kinases of the Src family, including Blk, Lyn, and Fyn.
Multiple models have been proposed how BCR-antigen binding induces phosphorylation, including conformational change of the receptor and aggregation of multiple receptors upon antigen binding. Tyrosine kinase Syk binds to and is activated by phosphorylated ITAMs and in turn phosphorylates scaffold protein BLNK on multiple sites. After phosphorylation, downstream signalling molecules are recruited to BLNK, which results in their activation and the transduction of the signal to the interior.
The B cell receptor in malignancy.
The B cell receptor has been shown to be involved in the pathogenesis of various B cell derived lymphoid cancers. Although it may be possible that stimulation by antigen binding contributes to the proliferation of malignant B cells, increasing evidence implicates antigen-independent self-association of BCRs as a key feature in a growing number of B cell neoplasias B cell receptor signalling is currently a therapeutic target in various lymphoid neoplasms.