B cells, along with T cells, are lymphocytes that bear antigen receptors that have been randomized for their binding specificity during development (see my earlier post). On the B Cell, the antigen receptor is aptly named: B Cell Receptor, or more commonly, BCR.
Like the T cell Receptor (TCR) on T Cells, the BCR is a transmembrane protein expressed on the plasma membrane, where it can bind by antigen. Unlike the TCR, B Cells are not ‘presented’ antigen by other cells in the context of an MHC molecule. Instead, B Cells ‘see’ antigens in their native state – imagine these as soluble toxins or cell-surface antigens on bacteria of viruses.
APC : T Cell Interaction vs Native Antigen : B Cell
Another difference between T Cell and B Cell activation is that T Cells become activated, but do not change their expression of their antigen receptor. B Cells, on the other hand, may react in one of several different ways. In general terms, this means differentiation into either Memory Cells or Plasma Cells.
Memory B Cells proliferate, but retain their membrane-bound receptors. This makes sense because the purpose of these cells is to lie in wait until antigen is seen again, so they need their receptors to ‘see’ it.
Plasma cells lose their membrane-bound receptors, but continue to express the same molecule in a soluble form called Antibody. In fact, they grow in size and fill with ER and Golgi Apparatus to handle the extreme output of protein that they begin producing (~2000 molecules / sec according to Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al. New York: Garland Science; 2002. ).
Antibody comes in a number of varieties, but all share a similar core structure as the one pictured to the right. It consists to two heavy chains and two light chains, creating two unique binding sites for antigen.
Events following B Cell Activation
Once cells become activated, they may either immediately become short-lived plasma cells (SLPCs) that secrete antibody identical to the BCR for a short time and then die off, or they may enter into Germinal Center (GC) Reactions. In the GC, B cells get T Cell help and compete for antigen in a poorly understood manner whilst undergoing hypermutation of the BCR’s antigen-binding site. This results in BCR / Antibodies with higher affinity (greater binding ability) for antigen that may then differentiate into either Long-Lived Plasma Cells (LLPCs) of memory cells. These several differentiation paths can be seen in the illustration below.
1. B Cells are activated as a result of crosslinking BCRs by native antigen
2. B cells do require help from T Cells to enter germinal center reactions and produce LLPCs and memory cells (although getting help was not discussed here)
3. B cells become activated and either start producing antibody right away as SLPCs or enter genrminal center reactions.
4. Once in a germinal center, B cells undergo hypermutation of the antigen-binding section of their BCR/Antibody.
5. Following the GC reaction, B cells bearing high-affinity BCR/antibody will differentiate into LLPCs or memory cells.