Q2. Outline the processes by which B cells become fully activated

B cell activation occurs in the secondary lymphoid organs such as the spleen and lymph nodes. After B cells mature in the bone marrow they migrate to the spleen and lymph nodes which receive a constant supply of antigen. B cell activation begins when the B cell bind to an antigen via its BCR. The antigen can either be free floating or presented by APCs such as macrophages or dendritic cells. The antigens can include proeins, glycoproteins, whole virus particles and whole bacterial cells. Mature B cells preferentially undergo T-cell dependant activation whilst marginal zone B cells and B1 B cells preferentially undergo T cell-independent activation.

B cell activation is enhanced through the activity of CD21, a surface receptor in complex with surface proteins CD19 and CD81 which are together known as the B cell coreceptor complex. When a BCR binds an antigen tagged with C3 complement protein, CD21 binds the C3 fragment, co-ligates with the bound BCR and signals are transducer to lower the activation threshold of the cell.

T cell-independent activation
Antigens that activate B cells with the help of T cells are known as T cell dependant antigens and include foreign proteins. They are unable to induce a humeral response in organisms that lack T cells. B cell response to these antigens takes multiple days, though antibodies generated have a higher affinity and are more functionally versatile than those generated rom T cell-independent activation.

Once a BCR binds to a TD antigen, the antigen is taken up into the B cell through receptor mediated endocytosis. The antigen is then degraded and presented to T cells as peptide pieces in complex with MHC-II molecules on the cell membrane. T helper cells that were activated through the same antigen recognise and bind these MHC-II peptide complexes through their TCR- this is called linked recognition. Intern adhesion molecules such as LFA-1 and ICAM-1 along with VCAM and VLA-4 increase the binding strength between the B cell and the T cell. Following TCR-MHC-II peptide binding, T cells express the surface protein CD40L as well as IL-4 and IL-21. CD40L serves as a co-stimulatory factor for B cell activation by binding the B cell surface receptor CD40, which promotes B cell proliferation, immunoglobulin class switching and sustains T cell growth and differentiation. CD30L on the activated T cell binds to CD30 on the B cell and promotes B cell activation.

Now activated, B cells participate in a 2 step differentiation process to yield both short lived plasma blasts for immediate protection and memory B cells for persistent protection.

T cell-independant activation
Antigens that activate B cells without T cell help are known as T cell-independent antigens and include foreign polysaccharides and unmethylated CpG DNA. They are names as such because they can induce a humroal response in organisms that lack T cells. B cell response to these antigens is rapid, although antibodies generated tend to have lower affinity and are less functionally versatile than those generated from T dependant activation.

As with TD antigens, B cells activated by TI antigens need additional signals to complete activation, but instead of receiving them from T cells, they are provided either by recognition and binding of a common microbial constituent to toll-like receptors or by extensive cross linking of BCRs to repeated eiptoped on a bacterial cell. T independent type I antigens such as LPS activate the TLRs expressed by B cels causing activation of either immature of mature B cells. T independent type II antigens can only activate mature B cells by cross linking a critical number of B-cell receptors on the surface of mature B cells. An example is BAFF which is secreted by dendritic cells to interact with the receptor TACI on the B cell.