B-cell receptor

Author:Prof. Dr. med. Peter Altmeyer

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Last updated on: 28.08.2021

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Synonym(s)

B cell antigen receptor; BCR

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DefinitionThis section has been translated automatically.

The B-cell receptor (BCR) is a multiprotein complex consisting of a membrane-bound immunoglobulin (antibody) and the transmembrane proteins Igα and Igβ. The BCR is a central component of the humoral immune response. It is specialized in the recognition of conformational epitopes of an antigen (= 3-D structure of an antigen). Furthermore, the BCR is capable of signal transduction and endocytosis. It thus initiates the antigen presentation of peptides by means of MHC-2 at the cell surface.

Defects in the BCR lead to impaired antibody production and signal transduction. Such defects can result in immunodeficiency, autoimmunity or malignancy (see also agammaglobulinemia).

General informationThis section has been translated automatically.

Maturation of the BCR: B cells arise in the bone marrow from lymphoid stem cells. In the early pro-B cells (see B lymphocyte below) somatic rearrangements of the gene segments encoding the immunoglobulins begin (see immunoglobulin-encoding genes). After rearrangement of the DNA, it is first transcribed into an RNA transcript, after processing by splicing into an mRNA and then translated into a heavy or light protein chain. This is always the µ-chain for IgM. This is also followed by gene rearrangements for the light chain L. Pairing of the heavy (H) and light (L) chains determines the specificity of the antibody. This results in only one immunoglobulin specificity per B cell clone (antibody specificity).

For these gene procedures, there is a high risk of frameshifts (shifts in the reading frame), of nonsense products, of chains that are not "pairable", which usually lead to the deletion of the B cell. Due to this high error rate, 2 out of 3 B cells are lost!

In addition to the actual specific immunoglobulin, the transmembrane proteins Igα and Igβ (CD79) are involved in the BCR. These components, non-covalently associated with the immunoglobulin, serve for signal transduction. They are linked to each other by a disulfide bridge to form heterodimers and have so-called immunoreceptor tyrosine activator sequences (ITAMs - see Immunoreceptor tyrosine-based activation motifs) .

Activation of the BCR and signal transduction: If 2 antibodies of the BCR receptor are cross-linked at the cell surface by binding an antigen (receptor aggregation), an activation of protein tyrosine kinases occurs. These phosphorylate the ITAMs of the Igα and Igβ molecules.

Signal transduction occurs via phospholipase C (PLC) and NFAT. Furthermore, via PIP3(phosphatidylinositol-3,4,5-triphosphate) and NF-κB, as well as via ERK. Signal transduction is further influenced by non-coding ribonucleic acids. Via NF-κB, phospholipase C (PLC) is activated by CD79a/b and other proteins. Subsequently, phospholipase C binds to cSMAC (central supramolecular activation cluster, a costimulatory signal transducer of the T cell receptor) and hydrolyzes PIP2 to PIP3 and diacylglycerol.

Costimulation: The activation pattern of the B-cell receptor is additionally influenced by costimulatory signals (costimulation). Thus, the B-cell coreceptor complex is involved in the activation. This consists of CD19, the complement receptor CR2(CD21) and CD81. The activating signal is transmitted to the interior of the B lymphocyte.

Essential for antibody production is that the activation of the B cell, also leads to its prompt proliferation. By alternative splicing, the BCR is now formed without an anchorage in the cell membrane. Soluble antibodies are formed from the membrane-bound BCR. The B cell has transformed into an antibody-secreting plasma cell.

Note(s)This section has been translated automatically.

Various mutations of the B-cell receptor are involved in the development of B-cell tumors. It is possible that a permanent activation of the BCR occurs.

Survival of circulating B cells requires signaling from both the BCR and B cell-activating factor (BAFF). This BCR prosurvival signaling is antigen-independent and is referred to as "tonic" signaling. It is distinct from the stronger signals triggered by binding of a cognate antigen, which lead to B cell activation and proliferation. BAFF transgenic mice and mice with B cell-specific BTK overexpression (CD19-hBtk) develop autoimmune pathology resembling human systemic lupus erythematosus (SLE) and primary Sjögren's syndrome.

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Last updated on: 28.08.2021