MCD – Immunology 5 - B-lymphocytes Anil Chopra 1. Describe the process of stimulation of individual B cells to divide and secrete antibody such as to generate immunity to a particular antigen (clonal selection). There are 2 types of adaptive response Humoral B-cells secreting antibodies. Cell Mediated T-cells secreting cytokines, lysis. B- cells are produced and mature in the bone marrow and travel to the lymphoid tissue in the circulation. They form part of the humoral adaptive immune response in the production of antibodies and memory cells. They only become activated by antigens. Mature B cells contain receptors specific for certain antigens. The B-cell antigen receptor is made up of 3 parts: - mIg - Ig - Ig The mIg part of the receptor contains the binding site (which binds to the antigen) known as the antigenic determinant or epitope. There are thousands of receptors on the surface of each B cell. 2. 2. Briefly outline the principles of immunoglobulin (Ig) gene rearrangement in the generation of diversity. We have a very large number of different antigens we can possibly encounter and so we have a very large number of different B-cell receptors; this is called the repertoire. This diversity is generated by the way in which the B-cell receptor is synthesised. Instead of there being one main functional gene that codes for the production of the B-cell receptor, there are many different genetic fragments darted about the genome on different chromosomes. When the B-cell is maturing, these gene segments are brought together in a random order and so a different B-cell receptor is synthesised in each cell. This is known as immunoglobulin gene rearrangement. 3. Outline the differences in antibody production during primary and secondary immune responses. When antigens are encountered, there are 2 main events that take place. The first is clonal selection. This is where the B-cell receptor first encounters the antigen; the antigen has “selected” that particular B-cell because of its specific receptor. However, in order for activation to occur their needs to be an accessory signal, either from Microbial constituents (results in production of IgM only and NO MEMORY). – Thymus independent activation. T-helper cell (results in production of all Ig classes and MEMORY) – Thymus dependent activation. In thymus independent activation, the B-cells “express” the antigens on their surface so that T-helper cells can bind to them and bring about the second response: Clonal expansion – this is where at particular B-cell makes many copies of itself – clones. These differentiate into memory cells and plasma cells. The plasma cells are the sites of: Antibody production – production of soluble B-cell receptors in response to the antigen. When the T-helper cells are activated, they release cytokines. Each of the different cytokines stimulates/inhibits the production of the different Ig isotypes. The memory cells that are produced have a long life span and form the basis of immunological memory. This means that if the person encounters the same antigen again, the secondary immune response will occur. In this response, antigen production is a lot faster and more IgG is produced. 4. Differentiate between monoclonal and polyclonal antibodies. Polyclonal Antibodies: these are antibodies that come from different B-cell lines. When an antigen enters the body, it has many different binding sites, where different B-cells can attach. When they do so, they produce different types of antibodies. This is a polyclonal response. Monoclonal antibodies: are ones that are derived from one B-cell clone. Myeloma = cancerous plasma cells that divides permanently without antigenic stimulation and secretes antibodies which are indistinguishable from normal antibody = myeloma proteins