The B‐Cell Surface Receptor For Antigen (BCR)
The B‐cell displays a transmembrane immunoglobulin on its surface
In Chapter 2 we discussed the cunning system by which an antigen can be led inexorably to its doom by activating B‐cells that are capable of making antibodies complementary in shape to itself through interacting with a copy of the antibody molecule on the lymphocyte surface. It will be recalled that binding of antigen to membrane antibody can activate the B‐cell and cause it to proliferate, followed by maturation into a clone of plasma cells secreting antibody specific for the inciting antigen (Figure 4.1a).
Figure 4.1 B‐cells and T‐cells “see” antigen in fundamentally different ways. (a) In the case of B‐cells, membrane‐bound immunoglobulin serves as the B‐cell receptor (BCR) for antigen. (b) T‐cells use distinct antigen receptors, which are also expressed at the plasma membrane, but T‐cell receptors (TCRs) cannot recognize free antigen as immunoglobulin can. The majority of T‐cells can only recognize antigen when presented within the peptide‐binding groove of an MHC molecule. Productive stimulation of the BCR or TCR results in activation of the receptor‐bearing lymphocyte, followed by clonal expansion and differentiation to effector cells.
Immunofluorescence staining of live B‐cells with labeled anti‐immunoglobulin (anti‐Ig) (e.g., Figure 2.8c) reveals the earliest membrane Ig to be of the IgM class. Each individual B‐cell is committed to the production of just one antibody specificity and so transcribes its individual rearranged VJCk (or λ) and VDJCμ genes. Ig can be either secreted or displayed on the B‐cell surface through differential splicing of the pre‐mRNA transcript encoding a particular immunoglobulin. The initial nuclear μ chain RNA transcript includes sequences coding for hydrophobic transmembrane regions that enable the IgM to sit in the membrane where it acts as the BCR, but if these are spliced out, the antibody molecules can be secreted in a soluble form (Figure 4.2).