BCR
BCR (B Cell Receptor) is the specific antigen receptor of the B cell.
It results from somatic recombination D-J then V-DJ of a heavy chain (µ then δ) and V-J of a light chain (κ or λ). BCR recognises a native antigen, necessarily extracellular, while signal transduction is ensured by a co-receptor. The plasma cell no longer has BCRs but secretes them in soluble form, also called immunoglobulins or antibodies. This is why BCR is also called “surface immunoglobulin”.
Tertiary structure of the receptor
BCR is a short transmembrane receptor of the immunoglobulin superfamily. It is a heterotetramer formed of two light chains (κ or λ) and two heavy chains (µ or δ) identical in pairs. Each of these chains is the product of a V(D)J recombination, whose polymorphism is concentrated in the V variable regions (VL and HL respectively) to provide maximum diversity at the paratope level (Fab), while retaining the structure responsible for initiating signal transduction (Fc).
H = Heavy, L = Light
CDR = Complementarity Determining Region
Hypervariable regions (CDR Complementarity Determining Region) of the light chain variable region recognise the antigen (CDR1, CDR2, and CDR3).
V(D)J recombination of the BCR
Each B cell synthesises a single type of BCR in very multiple copies. In other words, the B cell must only accept the recombination of a single chromosome 14 (H heavy chain), in accordance with the principle of allelic exclusion and of one of the two chromosomes 2 (κ light chain) or chromosomes 22 (λ light chain) in accordance with the principle of isotype exclusion.
A BCR is ALWAYS made up of two heavy chains and two identical light chains in pairs. It is not possible to have a BCR with two different heavy chains or two different light chains.
The recombination of the heavy chain occurs first. If this is complete, then the recombination of the light chain can begin. The precursor of the B cell can only survive and differentiate into a B cell if the rearrangements of a heavy chain and a light chain lead to the synthesis of a BCR (1st and 2nd checks within the bone marrow) (see B cell ontogeny).
| Chromosome | V | D | J | |
|---|---|---|---|---|
| Light chain κ | 22 | ≈35 | 0 | 5 (but multiple alleles) |
| Light chain λ | 2 | ≈35 | 0 | 5 |
| Heavy chain | 14 | ≈35 | ≈25 | 6 |
Co-receptors
CD79 ensures signal transduction
CD79 is an Igα/Igβ heterodimer whose long intra-cytoplasmic part (unlike the BCR which only has 3 intracellular amino acids) allows signal transduction.
CD21 ensures the stability of the interaction
The engagement of CD21, although optional, makes it possible to stabilise the interaction between the BCR and the antigen via CD3d, a product of the complement cascade.
Engagement and downstream pathways
Once the BCR engages in the interaction with the native antigen, signal transduction takes place which leads to the activation of downstream molecular pathways (see B cell activation).
What needs to be remembered
The BCR is the immunoreceptor carried by B cells, and each of them carries on its surface the same BCR in very numerous copies. The BCR is the product of somatic V(D)J recombination, which makes it possible to generate an infinite number of receptors to respond to the infinite number of antigens present in our environment. After being activated, the B cell can transform into a plasma cell: it then no longer expresses BCR on its surface but secretes them, these are then immunoglobulins, also called antibodies.
