To explain:
The importance of genetic recombination and post recombination events related to diversity in antibodies
Concept introduction:
Antibodies are the potential receptors that can recognize unique aspects of antigen present on the pathogen. Antibodies are produced by the differentiation of B cells into plasma cells. Based on the physical, chemical, and immunological properties, antibodies are classified into 5 classes namely IgG, IgA, IgM, IgE, and IgA. All the antibodies share a common structural similarity by having 2 light and 2 heavy chains. Each light and heavy chain are further classified into “constant (C) and variable (V) domains”. Disulphide bonds connect one light chain with another heavy chain. Each heavy and light chain is derived from the combination of several gene fragments generated after several events of recombination.
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Brock Biology of Microorganisms (15th Edition)
- In rare instances, B cells can be found that have two immunoglobulin light chain alleles, both of which are rearranged in frame, and can encode functional light chain proteins. Yet, on the surface of the B cell, only one of the two light chain proteins is detected in the membrane-bound immunoglobulin receptor. The reason these rare cells have two functional light chain rearrangements but only express one of the two light chains as part of the B-cell receptor is: One of the two light chains is formed from rearrangement of a V gene segment that is a pseudogene. One of the two light chain proteins doesn’t form a stable complex with the heavy chain expressed in this cell. One of the two light chain alleles is not transcribed efficiently, and produces only low levels of protein. One of the two light chain alleles uses a V gene segment that is not targeted very often by the RAG recombinase. One of the two light chains is rapidly degraded after synthesis due to improper folding.arrow_forwardSuppose that a particular species of vertebrate animal has immunoglobulin heavy-chain genes that include 55 V segments, 21 D segments, and 8 J segments, and has immunoglobulin light-chain genes that include 41 V segments and 6 J segments. How many different immunoglobulin structures could be produced by mature B-lymphocytes? (Assume that segments are spliced without any junctional variation or imprecision).arrow_forwardWhen a mixture of different IgG antibody proteins are treated with the enzyme papain, each antibody is cleaved into three roughly equal size fragments. From each original antibody, two of the three fragments are identical to each other, and represent the ‘arms’ of the antibody ‘Y’. These fragments are known as Fab fragments. The third fragment is known as the Fc region, because this fragment will crystallize when purified. The reason a mixture of Fc fragments will crystallize is because: It is the only part of the antibody protein that can easily be purified at the high concentrations needed for crystallization. It has no disulfide bonds holding the domains together, as disulfide bonds will inhibit crystallization. It is the only fragment of the antibody that still has disulfide bonds, so it remains intact during the crystallization process. The Fc fragments of IgG are much more water soluble than the Fab fragments. All Fc fragments generated from a mixture of IgG molecules have the…arrow_forward
- V/D/J recombination frequently yields a gene whose mRNA cannot be successfully translated into an immunoglobulin chain. What aspect of somatic recombination is likely to produce nonproductive gene rearrangement?arrow_forwardA wild-type mouse that is heterozygous for two immunoglobulin heavy chain alleles (IgHa/b) generates the population of B cells shown on the left of the figure below. A mouse strain, also IgHa/b, carries an inactivating mutation in the VpreB gene. In addition to producing fewer mature B cells than the wild-type mice, the VpreB-deficient mice generate B cells as shown on the right. What is the explanation of the difference seen between the wild-type and the VpreB-mutant B cells?arrow_forwardThe immunoglobulin molecules of a particular mammalian species have kappa and lambda light chains and heavy chains. The kappa gene consists of 250 V and 8 J segments. The lambda gene contains 200 V and 4 J segments. The gene for the heavy chain consists of 300 V, 8 J, and 4 D segments. If just somatic recombination and random combinations of light and heavy chains are taken into consideration, how many different types of antibodies can be produced by this species?arrow_forward
- An important mechanism for generating diversity in immunoglobulin light chain V-region sequences is based on the fact that the RAG recombinase generates hairpin structures, rather than blunt ends, at the cleavage sites between the recombination signal sequences and the coding sequences. Explain how this mechanism generates diversity at the junctions.arrow_forwardCan you please help me by drawing a serie of schematic figures that demonstrates the information in the paragraph below. The carboxy terminus of the p53 protein acts as an allosteric regulator of sequence-specific DNA binding. This was demonstrated initially by Hupp et al. (1992) using a bacterially expressed protein. Recombinant bacterial p53 bound poorly to DNA, and binding could be enhanced by the addition of antibodies specific to the C-terminal region of the protein. Phosphorylation of Ser315 and Ser392 within this domain also enhance sequence-specific DNA binding. Dephosphorylation of Ser376 of p53 after IR allows the association of 14-3-3 proteins with the C terminus of the protein (Waterman et al., 1998). Stavridi et al. (2001) demonstrate that this interaction is required for p53 to activate the downstream gene, p21waf1/cip1, and for the G1 cell cycle checkpoint arrest response. Interestingly, this dephosphorylation event seems to be ATM-dependent, possibly by a phosphatase…arrow_forwardB cells are specialized blood cells that secrete antibodies. Normally, human blood has millions of differenttypes of B cells making millions of different kinds ofantibody molecules. This variety occurs because, as described in the Fast Forward Box in Chapter 13 entitledProgrammed DNA Rearrangements and the ImmuneSystem, antibody genes undergo rearrangements in theprecursors of B cells. Individual B cell precursorsrearrange their antibody genes in different ways.In the blood of patients with cancers called B celllymphomas, almost all of the antibody molecules areall of one type, but this single type of antibody isdifferent in different lymphoma patients.a. Based on this information, provide a brief description of the genesis of B cell lymphomas, focusingon the cells that are overproliferating.arrow_forward
- Variable addition and subtraction of nucleotides at the junctions between gene segments contributes to the diversity of [Qi] the third hypervariable region. The addition and subtraction of nucleotides at the junctions between V, D, and J gene segments creates antibody proteins with wide variations in the numbers of amino acids in their CDR3 regions. This variability in CDR3 length is important as: Overall variability in CDR3 sequence is needed to create a sufficiently diverse antibody repertoire. The CDR3 region is more important in binding antigen than the CDR1 and CDR2 regions are. Some light chains bind better to heavy chains with longer CDR3 region sequences. Longer CDR3 sequences generally create antibodies with higher affinity for the antigen. Some antibodies bind relatively flat surfaces and others bind deep clefts in the antigen.arrow_forwardSeveral vaccines against viral infections are made by isolating purified surface proteins of the viral particle, mixing them with an adjuvant to stimulate an innate immune response, and injecting the mixture into people. Two examples of this are the vaccine against Hepatitis B virus, and the vaccine against Human Papilloma Virus (the ‘cervical cancer’ vaccine). One interesting property of vaccines of this type (known as ‘subunit vaccines’) is that there is a requirement for a CD4 T cell response to the vaccine antigen in order to generate antibodies to the innocuous protein in the vaccine. In the case of the Hepatitis B vaccine, the viral protein included in the vaccine is the Hepatitis B surface antigen (HepB-SAg), a protein that is approximately 200 amino acids in length. The graph in Figure Q4.27 shows the data from immunizing individuals with this vaccine, and monitoring their production of protective antibody responses to the viral protein. a) What results would be predicted if…arrow_forwardAtaxia-telangiectasis (ATM) is a rare genetic neurodegenerative disease. About 20% of people with ATM develop acute lymphocytic leukemia or lymphoma, cancers of the immune-system cells. Cells in many of these cancers exhibit chromosome rearrangements, with chromosome breaks occurring at antibody and T-cell-receptor genes (A. L. Bredemeyer et al. 2006. Nature 442:466–470). Many people with ATM also have a weakened immune system, which makes them susceptible to respiratory infections. Research has shown that the locus that causes ATM has a role in the repair of double-strand breaks. Explain why people who have a genetic defect in the repair of doublestrand breaks might have a high incidence of chromosome rearrangements in their immune-system cells and why their immune systems might be weakened.arrow_forward
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