B-cell receptor
The B-cell receptor (BCR) is a transmembrane protein on the surface of a
The receptor's binding
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
The B-cell receptor is composed of two parts:
- A membrane-bound immunoglobulin molecule of one isotype (IgD, IgM, IgA, IgG, or IgE). With the exception of the presence of a transmembrane alpha-helix, these are identical to their secreted forms.
- Signal transduction moiety: a disulfide bridges. Each member of the dimer spans the plasma membrane and has a cytoplasmic tail bearing an immunoreceptor tyrosine-based activation motif (ITAM).[6][7]
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 membrane 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.[1][7]
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 when there is no specific antigen. This is because when cells do not meet any antigen within this time, they will go through apoptosis.[6] It is notable that in the peripheral circulation, apoptosis is important in maintaining an optimal circulation of B-lymphocytes.[8][9] In structure, the BCR for antigens are almost identical to secreted antibodies.[1][5] 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 BCR is similar for all receptors of the
- IKK/NF-κB Transcription Factor Pathway: IkB(an inhibitor of and bound to NF-κB), which induces its destruction by marking it for proteolytic degradation, freeing cytosolic NF-κB. NF-κB then migrates to the nucleus to bind to DNA at specific response elements, causing recruitment of transcription molecules and beginning the transcription process.
- Ligand binding to the BCR also leads to the phosphorylation of the protein BCAP. This leads to the binding and activation of several proteins with phosphotyrosine-binding SH2 domains. One of these proteins is PI3K. Activation of PI3K leads to PIP2 phosphorylation, forming PIP3. Proteins with PH (Pleckstrin homology) domains can bind to the newly created PIP3 and become activated. These include proteins of the FoxO family, which stimulate cell cycle progression, and protein kinase D, which enhances glucose metabolism. Another important protein with a PH domain is Bam32. This recruits and activates small GTPases such as Rac1 and Cdc42. These, in turn, are responsible for the cytoskeletal changes associated with BCR activation by modifying actin polymerisation.
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,[14] increasing evidence implicates antigen-independent self-association of BCRs as a key feature in a growing number of B cell neoplasias.[15][16][17][18] B cell receptor signalling is currently a therapeutic target in various lymphoid neoplasms.[19] It has been shown that BCR signaling is synchronised with CD40 pathway activation provided by B-T cell interactions, and this seems to be essential to trigger proliferation of leukemic B cells.[citation needed]
See also
References
- ^ ISBN 978-1429219198.
- ISBN 978-3642038570.
- ^ ISBN 978-0-12-394296-8.
- ^ PMID 15219998.
- ^ ISBN 978-1441918871.
- ^ ISBN 978-0815341017.
- ^ ISBN 978-1555812461.
- ^ PMID 26802217.
- ^ ISBN 978-0815344322.
- PMID 14632637.
- PMID 23046135.
- PMID 22269039.
- ISBN 0815342438.
- PMID 13813891.
- PMID 2284498.
- PMID 8548286.
- PMID 20054396.
- PMID 22885698.
- PMID 22715122.
External links
- B-Cell+Antigen+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)