1. Pre-B cell receptor’s light chain is replaced with a surrogate light chain [ (VpreB (variable region) and λ5 (constant region) ]. It is also on the surface with Ig and Ig, and these are the signaling molecules. This occurs in transitional stage from late pro-B cell to the large pre-B cell stage. In the Large pre-B cell, the chain has already been made. The pre-B cell receptor sends the signal that allows the pro-B cell to become and pre-B cell. For test purposes: the pre-B cell receptor has to make it to the surface and has to associate with some sort of ligand. Without a functional pre-B cell receptor, the B cell dies by apoptosis. It also prevents B cells from making more than functional heavy chain (allelic exclusion). The synthesis of the chain and the assembly of a pre-B cell receptor stops and degrades the RAG genes. Slide 29.
2. Stromal cells provide specialized microenvironments for B cells at various stages of maturation. B cells at a later stage of maturation require IL-7 to stimulate growth and proliferation. IL-7 is there from late pro-B until pre-B cell stage. Picture on page 162
3. No allelic exclusion gives heterogeneous B-cell receptors with low-avidity binding. B cells with allelic exclusion 1000-fold more effective than those made without allelic exclusion.
4. Allelic exclusion is only allows one heavy chain and one light chain, stops the production of a second heavy chain. Allelic exclusion gives homogeneous B-cell receptors with high-avidity binding.
5. D and J join in the early pro-B cell. V joins with DJ in the late pro-B cell. A finalized chain defines a large pre-B cell. Light chain rearrangement occurs in the small pre-B cell, joining V and J gene segments. Successful light chain rearrangement and the expression of IgM on the cell surface define the immature B cell.
6. Surrogate light chain consists of VpreB and 5. VpreB serves as the variable region of the light chain and the 5 serves as the constant region of the light chain. The chain must demonstrate the ability to combine with Ig light chain but at this stage the light chain hasn’t been rearranged, so it synthesizes the surrogate light chain.
7. Ig and Ig are part of the pre-B cell receptor and are used as signaling molecules. The entire pre-B cell receptor sends the signal that allows a pro-B cell to become a pre-B cell.
8. An immature B cell has the heavy and light chain genes already rearranged and with IgM on its surface. After reaching the IgM+ immature stage in the bone marrow, these immature B cells migrate to secondary lymphoid tissues (such as the spleen, lymph nodes, Peyer's patches, etc.) where they are called transitional B cells, and some of these cells differentiate into mature B lymphocytes. Mature B cells have IgM and IgD on the surface after alternative mRNA splicing. Immature B cells have high IgM and low IgD and mature B cells have low IgM and high IgD.
9. In the Large pre-B cell the chain is officially made. Large pre-B cells proliferate, producing small pre-B cells in which rearrangement of the light-chain gene occurs. Shuts down RAG-1 and RAG-2, tagged RAG-2 for destruction, closed up the heavy chain genes so that access is not granted to RAG 1 and 2; so we have allelic exclusion - only having only ONE heavy chain gene.
10. Clonal deletion is when a B cell dies by apoptosis and are phagocytosed by macrophages. These cells die because they have exhausted all possibilities of light-chain gene rearrangements without ever gaining a receptor that is not self-reactive. Anergic cells make both IgD and IgM, but unlike in mature B cells, the IgM is prevented from assembling a functional B-cell receptor and is largely retained within the cell. They have a shorter life span than mature B cells. Anergic B cells fail to reach a primary follicle and instead concentrate at the boundary between the follicle and the T-cell zone. This…