Somatic hypermutations and Class Switch Recombination.
When B cells have successfully rearranged their IgH and IgL loci and express a BCR they will leave the bone marrow as immature B cells and become transitional B cells that migrate to secondary lymphoid tissues. In the lymphoid tissues B cells may be exposed to antigen and the initial antigen encounter will initiate a dynamic cascade of cell signalling events that ultimately promotes cellular activation and proliferation57-60. In the secondary lymphoid organs this area of B cell expansion is a visible structure and termed the germinal centre (GC)61. As B cells divide, their receptor undergoes somatic hypermutation (SHM); a mechanism whereby the IgH and IgL genes are hypermutated and fine
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SHM occurs by two mechanisms: 1) DNA replication reads the uracil as a thymidine and pairs it with an adenine which results in a C to T or G to A transition. This type of mutation only requires AID activity68, 69. 2) Uracil is a pyrimidine normally found in RNA and the base-excision repair system will therefore attempt to correct the mistake by removing the uracil. This creates an abasic site in the DNA strand. The removal of the uracil is executed by an enzyme called uracil N-glycosylase (UNG)70, 71. In the abasic site a random nucleotide may be inserted leading to both transitions (G:C into A:T) and transversions (G:C into C:G)68. Ultimately, for both mechanisms it is the misreading of a low fidelity polymerase that is responsible for the introduction of the point mutation72, 73. AID only binds single stranded (ss) DNA and thus only functions on actively transcribed alleles where transcription temporarily separates of the two DNA strands within the transcription bubble74-76. Sequencing studies support this in that mutations only occur downstream of the VH-gene promoter suggesting the importance of this promoter for AID activity. It is hypothesized that AID is recruited
d. In 3.a (above) you mutated one letter. What role do you think the redundancy of the genetic code plays in this type of change?
The vital components and techniques of gene cloning are as follows, the DNA sequence that contains the desired gene (EZH2) is amplified by Polymerase chain reaction. PCR was established by Kary Mullis in 1985, popularly known to amplify target sequences of DNA (EZH2) to a billion fold in several hours using thermophilic polymerases (Taq) ,primers and other cofactors (Sambrook and Russell, 2001). Three crucial steps are involved which are Denaturation (at 95°), Annealing of the forward and reverse primers (55-65°) and lastly primer extension (at 72°). After amplification the desired sequence is integrated into the circular vector (pbluescript) forming the recombinant molecule. For the compatibility of the insert and vector, both were digested with (EcoR1) so the same cohesive ends are generated in both, making it easier to ligate. EcoR1 is a restriction enzyme that belongs to the type II endonuclease class which cuts within dsDNA at its recognition site “GAATTC” (Clark 2010; Sambrook and Russell, 2001).
c is incorrect because AID switches cytosines for uracils, which causes mutations. It also converts IgM to
In B-cells the quality control checks are done with a surrogate light chain to make sure that the heavy chain is functional. During the pro-B-cell stage the heavy chain assembles with the surrogate light chain and Igβ. If it is successful, then it shows it forms a functional pre-B-cell and signals to shut down gene rearrangement at the heavy chain. If it cannot do that then the cell will not get the signal to survive and it will die. Next the B-cell generates a light chain gene diversity in pre-B-cells then is checked for its functional B-cell receptor. Without functional B-cell receptor it will not get the signal to survive and will die.
B-cells develop from pluripotent hematopoietic stem cells, which give rise to lymphoid progenitor cells in the bone marrow. These stem cells have become Pro-B cells when they have begun to express B-cell marker proteins such as CD34 and rearrange the genes that code for the
Tissue sample presented with large population of B cells, labelled with CD20, in follicles and macrophages labelled with CD68 were also visible in the intrafollicular zone, both are indicative of a humoral immune response.
Some chemicals can induce the modification of bases: Note: Conversion of C to U will result in a C:G to A:T mutation after replication
In the synapsis step, the Rad51-ssDNA filament (presynaptic filament) performs homology search and DNA strand invasion on a homologous region of another duplex, which results in the formation of a displacement loop (D-loop) [40]. In the post-synapsis stage of HR the invading 3′ end of the D-loop primes DNA synthesis by a DNA polymerase, which extends the D-loop enabling the second 3’ single strand terminal end of the DSB to base-pair with it - a process that is called second end capture. Once captured the second end can itself prime DNA synthesis, and the result of these “DNA transactions” is the covalent linkage of the recombining DNA molecules via two HJs. Depending on how the HJs are processed to form mature recombinant products three sub-pathways of HR are distinguished. In the canonical DSBR model the two HJs (doubleHJ/dHJ) can move along the DNA by a process called branch migration, which extends or limits the region of DNA heteroduplex formed by strand exchange catalyzed in the second step. Subsequently, dHJ intermediate could be resolved by endonucleases such as the Mus81-Eme1/Mms4 complex, Slx1-Slx4 and the GEN1/Yen1, resulting in the formation of either crossovers (CO) or non-crossover (NCO) recombinants depending on the orientation in which each HJ is cleaved
CEP has been linked to a variety of loss of function mutations on the UROS gene including missense, nonsense, splice-site and small intragenic deletions. However the majority of these mutations occur so rarely that the most common pathogenic mutations are considered to be missense mutations, specifically a C to T change at nucleotide 197, substituting an alanine for valine at residue 66 (A66V) and a T to C change at nucleotide 217, substituting a cysteine to arginine
The organs that make up the lymphatic and immune system are the tonsils, spleen, thymus gland, lymph nodes, and lymphatic vessels. White blood cells (leukocytes), red blood cells (erythrocytes), plasma, and platelets (thrombocytes) make up the blood. Lymphocytes are leukocytes (white blood cells) that help the body fight off diseases. Two types of lymphocytes are B cells and T cells. Lymphocytes recognize antigens, or foreign substances/matter, in the body. Lymphocytes are a classification of agranulocytes, or cells (-cytes) without (a-) granules (granul/o) in the cytoplasm. B cells are created from stem cells, which are located in the bone marrow. B cells respond to antigens by becoming plasma cells. These plasma cells then create antibodies. Memory B cells produce a stronger response with the next exposure to the antigen. B cells fight off infection and bacteria while T cells defend against viruses and cancer cells. A hormone created by the thymus gland called thymosin changes lymphocytes into T cells. The thymus gland is active when you are a child and slowly shrinks, as you get older. T cells bind to the antigens on the cells and directly attack them. T cells secrete lymphokines that increase T cell production and directly kill cells with antigens. There are three types of T cells: cytotoxic T cells, helper T cells, and memory T cells.
In conclusion, the experiments showed that my hypothesis for salinity is not supported because hot water is less dense than cold water, therefore, the hot water floated on the cold water. Hot air floats and cold air sinks which creates wind so the same reasoning could be used for hot water floats and cold water sinks. The research talked about how ice is less dense than water but never directly stated that cold water was less than water also. An assumption that the same thing applied to cold water was made when creating the hypothesis. On the other hand, the results supported the hypothesis for temperature, showing how salt water would remain on the bottom or move there and fresh water would stay on the top or move there as well. Research
To understand the pathophysiology of MM, it is essential to understand the concept of B-cell maturation into plasma cells that release proteins called immunoglobulins (Kelly et al, 2010). Lymphoid stem cells in the bone marrow develop into either T or B lymphocytes (Kelly et al, 2010). The B lymphocyte is responsible for humoral immunity and can be identified by the presence of a membrane immunoglobulin (Sommer, 2009). There are five classes of immunoglobulins: IgG, IgA, IgM, IgD, and IgE (Sommer, 2009). Each immunoglobulin has “two identical light (L) chains and two identical heavy (H) chains to form a ‘Y’-shaped molecule” (Sommer, 2009, p. 365). The light chains are termed kappa or lambda and the heavy chains define the five classes of immunoglobulins (Kelly et al, 2010). Myeloma occurs when there is an overproduction of one of these immunoglobulins (Kelly et al, 2010). The immunoglobulin that
The expressivity and penetrance of FA are largely based on the number and type of subtypes present. It was found that a large amount of the subtypes of FA actually interact with each other in one form or another to cause reactions and abnormalities in many of the pathways that are critical to the replication and regulation of DNA in each of the cells pathways. Interestingly enough, if just one of the subtypes is not present, then the expression of the interference is not as extreme as it could be if all of the subtypes needed for a category were present.
February 2015 I woke up feeling the need to vomit and I had a bad headache that night I barely got any sleep the next morning my mom made an appointment we got to the doctor's office, with a series of tests they sent me to the hospital to get more tests done the tests took forever later we found out that I needed to go into surgery because my VP shunt broke a day later I was released and on the road to recovery.
I am really interested in applying for the HND sports coaching course because since a young age I have always been interested in how the human body works and how to maximize the effects exercise has on your body. I feel going onto the HND would really help enhance my coaching skills and really benefit me, not only in the short term but also in the long term, it would really help me further my coaching experience and to also get me ready and prepared for my career path and goals, both in the short term and the long term. I really enjoy working with and coaching children of all ages and I take great pride when coaching them, especially when I see the children develop throughout my sessions and over the following weeks. I have always had a keen