Immunology: MCQs on Immunoglobulin Gene Structure and Diversity (Answers with explanation)

Immunoglobulins, also known as antibodies, are proteins produced by the immune system to recognize and neutralize foreign substances such as bacteria, viruses, and toxins. The structure and genetic diversity of immunoglobulins play a critical role in their ability to protect the body against a wide range of pathogens. 
The structure of an immunoglobulin molecule consists of two identical heavy chains and two identical light chains, which are linked together by disulfide bonds. Each chain contains a variable region and a constant region. The variable region is responsible for binding to a specific antigen, while the constant region determines the effector function of the antibody, such as activating complement or recruiting immune cells.
The genetic diversity of immunoglobulins is generated through a process called somatic recombination. This process involves the rearrangement of gene segments encoding the variable region of the heavy and light chains, resulting in a vast repertoire of different antigen-binding sites. Additionally, somatic hypermutation introduces point mutations in the variable region, further increasing the diversity of the immunoglobulin repertoire.
The diversity of immunoglobulin genes is encoded in the germline DNA of B cells, the immune cells that produce antibodies. During B cell development, the germline DNA undergoes a series of genetic rearrangements to generate a diverse repertoire of antibody genes. This process is regulated by a complex set of genetic and epigenetic mechanisms, which ensure that each B cell produces a unique immunoglobulin molecule with a specific antigen-binding site.
In summary, the structure and genetic diversity of immunoglobulins are critical for their ability to recognize and neutralize a wide range of pathogens. The complex process of somatic recombination and somatic hypermutation ensures that the immune system can generate a vast repertoire of antibody molecules, each with a unique antigen-binding site. This diversity is encoded in the germline DNA of B cells and is regulated by a complex set of genetic and epigenetic mechanisms.

Immunoglobulin Structure and Genetic Diversity: Multiple Choice Questions

1) Immunoglobulins are produced by plasma cells differentiated from plasma cells and committed towards specific antibodies. 
Which of the following statement is TRUE regarding the genes for these antibodies?
a) The specificity of the antibodies is predetermined by the set of genes before exposure to antigen.
b) The diversity is governed by the set of separate genes i.e. each gene encodes for its specific antibodies.
c) The antibody is encoded by the multi-gene family for the heavy and light chain and its rearrangement confers the diversity.
d) None of the above

2) The light chains of the immunoglobulins are encoded by either kappa or lambda genes. These genes consist of different segments that encode for the variable and constant domain. 
They are:
a) C-J-V
b) V-J-C
c) J-V-C
d) None of the above

3) The heavy chains of the immunoglobulins are encoded by the genes consisting of different DNA segments that encode for the variable, and the constant region. 
They are:
a) C-J-D-V
b) C-D-J-V
c) V-J-D-C
d) V-D-J-C

4) The rearrangement of antibody genes is an orderly process. During the gene expression, which of the following segment undergo the first gene arrangement?
a) The heavy chain constant region that determines the isotype
b) Heavy chain variable region that determines antibody specificity
c) The light chain constant region that provides the backbone
d) Light chain variable region that determines antibody specificity

5) Which of the following is the sequential process of gene arrangement of kappa light chain of antibody?
a) VJ joining --> Transcription --> Alternative RNA splicing --> VJC joining --> Translation
b) Transcription --> VJ joining --> Alternative RNA splicing --> VJC joining --> Translation
c) Transcription --> Alternative RNA splicing --> VJ joining --> VJC joining --> Translation
d) None of the above

6) Which of the following is the sequential process of gene arrangement of the heavy chain of antibodies?
a) Transcription --> DJ- joining --> VDJ joining -->Alternative RNA splicing --> Translation
b) VJ- joining --> VDJ joining -->Transcription --> Alternative RNA splicing --> Translation
c) DJ- joining --> VDJ joining -->Transcription --> Alternative RNA splicing --> Translation
d) None of the above

7) In humans, the gene that encodes for the heavy chain of immunoglobulin is present in chromosomes:
a) 2
b) 14
c) 22
d) None of the above

8) In humans, the genes that encode for the kappa light chain of immunoglobulin is present in chromosome:
a) 2
b) 14
c) 22
d) None of the above

9) In humans, the genes that encode for lambda light chain of immunoglobulin is present in chromosome:
a) 2
b) 14
c) 22
d) None of the above

10) In mice, the genes that encode for the heavy chain of the immunoglobulin is present in chromosome:
a) 6
b) 12
c) 16
d) None of the above

11) The recombination and gene arrangement of the immunoglobulin gene occurs at the site which consists of a unique conserved sequence known as a recombination signal sequence. 
It consists of:
a) GC-rich nucleotide sequence
b) AT-rich nucleotide sequence
c) AG-rich nucleotide sequence
d) Poly A nucleotide sequence

12) The recombination and gene arrangement requires two proteins known as RAG-1 and RAG-2. What is the function of RAG-1 &RAG-2 protein?
a) They catalyze the cleavage of one strand of the DNA
b) They catalyze the cleavage of both strands of the DNA
c) They catalyze the addition of 15 nucleotides in the junction
d) None of the above

13) In membrane-bound IgM molecules, the transmembrane and cytoplasmic segments are encoded by which of the following exons?
a) CH3 & CH4 exons
b) M1 and M2 exons
c) M1 and C1 exons
d) None of the above

14) Which of the following antibodies may be co-expressed by the B-cells?
a) IgM and IgA
b) IgM and IgD
c) IgG and IgD
d) IgG and IgE

15) The assembly of light and heavy chains into disulfide and glycosylated immunoglobulin occurs in the rough endoplasmic reticulum. 
What is the order of assembly for IgM?
a) Assembly of two heavy chains (HH) followed by light chain (LL) and H2L2
b) Assembly of one heavy chain and light (HL) followed by H2L2
c) Assembly of two heavy chains (HH) followed by light chain H2L and H2L2
d) All of the above

16) The assembly of light and heavy chains into disulfide and glycosylated immunoglobulin occurs in the rough endoplasmic reticulum. 
What is the order of assembly for IgG?
a) Assembly of two heavy chains (HH) followed by light chain (LL) and H2L2
b) Assembly of one heavy chain and light (HL) followed by H2L2
c) Assembly of two heavy chains (HH) followed by light chain H2L and H2L2
d) All of the above

17) Which of the following transcription factor binds to the immunoglobulin promoter?
a) E2B
b) Myc
c) Rb2
d) Oct1

18) Chimeric humanized monoclonal antibodies are generated using
a) Hybridoma technology
b) Recombinant DNA technology
c) Southern blot
d) Hyperimmunization

19) Which of the following results in the diversity of the antibodies?
a) Somatic hypermutation
d) Association of light and heavy chain
c) V-D-J joining
d) All of the above

20) Which of the following is true regarding the expression of immunoglobin?
a) The genes from both parents are expressed in a cell
b) The genes from one parent are expressed in a cell
c) The H and L genes are randomly derived from either parent
d) None of the above


Multiple Choice Questions Answers and Explanation:-
1-c) The antibody is encoded by the multi-gene family for the heavy and light chain and its rearrangement confers the diversity 
Immunoglobulins are proteins that are produced by plasma cells, which are differentiated from B cells. Each B cell has multiple copies of the genes that encode the heavy and light chains of the immunoglobulin molecule. These genes are arranged in a multi-gene family, and the process of somatic recombination rearranges the genes in each B cell to generate a unique sequence that encodes a specific antibody. This process of somatic recombination is a major mechanism for generating the diversity of immunoglobulins. Therefore, the correct statement is that the antibody is encoded by the multi-gene family for the heavy and light chain, and its rearrangement confers diversity.

2-b) V-J-C
The light chains of the immunoglobulins are encoded by either kappa or lambda genes, and these genes consist of different segments that encode for the variable and constant domains. The gene segments for the light chain include a variable (V) segment, a joining (J) segment, and a constant (C) segment. During B cell development, the V and J segments undergo somatic recombination to generate a unique sequence that encodes the variable domain of the light chain, which is responsible for antigen binding. The rearranged V and J segments are then joined with the C segment to form a complete light chain gene.

3-d) V-D-J-C
The heavy chains of the immunoglobulins are encoded by genes that consist of different segments that encode for the variable and constant regions. The gene segments for the heavy chain include a variable (V) segment, a diversity (D) segment, a joining (J) segment, and a constant (C) segment. During B cell development, the V, D, and J segments undergo somatic recombination to generate a unique sequence that encodes the variable domain of the heavy chain, which is responsible for antigen binding. The rearranged V, D, and J segments are then joined with the C segment to form a complete heavy chain gene.

4-b) Heavy chain variable region that determines antibody specificity
During B cell development, the rearrangement of the genes that encode the immunoglobulin heavy and light chains is an orderly process. The rearrangement of the immunoglobulin genes begins with the variable region of the light chain. Specifically, the V and J segments of the light chain gene undergo somatic recombination to generate a unique sequence that encodes the variable domain of the light chain, which is responsible for antigen binding. Once the light chain variable region is rearranged, it is then expressed on the surface of the B cell in association with a surrogate light chain. This forms the pre-B cell receptor, which signals the B cell to undergo heavy chain rearrangement.
Next, the heavy chain gene undergoes somatic recombination of the V, D, and J segments to generate a unique sequence that encodes the variable domain of the heavy chain. Once the heavy chain variable region is rearranged, it is expressed on the surface of the B cell in association with the light chain. This forms the B cell receptor, which is capable of recognizing and binding to specific antigens.

5-a) VJ joining --> Transcription --> Alternative RNA splicing --> VJC joining --> Translation
The process of gene arrangement for the kappa light chain of antibodies involves a sequential process of gene rearrangement, transcription, and translation. During B cell development, the V and J segments of the kappa light chain gene undergo somatic recombination to generate a unique sequence that encodes the variable domain of the light chain. This rearranged gene is then transcribed into mRNA.
The mRNA undergoes alternative RNA splicing to remove any non-coding introns and produce a mature mRNA molecule that encodes the complete variable domain of the kappa light chain. This mature mRNA then undergoes translation, where the amino acid sequence of the kappa light chain is synthesized.
Finally, the VJC segments are joined to complete the coding sequence for the complete kappa light chain. The completed kappa light chain then forms a functional immunoglobulin molecule with the heavy chain to form the B cell receptor.
Therefore, the correct sequential process of gene arrangement for the kappa light chain of antibodies is transcription --> VJ joining --> alternative RNA splicing --> VJC joining --> translation

6-c) Transcription --> Alternative RNA splicing --> VJ joining --> VJC joining --> Translation 
During the gene arrangement process of the heavy chain, the D and J segments rearrange first to form a DJ segment. Next, the DJ segment rearranges with a V segment to form a VDJ rearranged gene. The VDJ rearranged gene is then transcribed into mRNA, which undergoes alternative RNA splicing and translation to produce a functional heavy chain.

7-b) 14 
In humans, the gene that encodes for the heavy chain of immunoglobulin is located on chromosome 14q32.33, which contains the immunoglobulin heavy chain gene cluster. This cluster includes several genes that encode for the different isotypes of immunoglobulin heavy chains, including IgM, IgD, IgG, IgA, and IgE.

8-a) 2
In humans, the genes that encode for the kappa light chain of immunoglobulin are present on chromosome 2. The kappa light chain gene locus on chromosome 2 contains the variable (V) and joining (J) gene segments, as well as the constant (C) gene segment. The arrangement of these gene segments results in the expression of a functional kappa light chain.

9-c) 22, 
In humans, the genes that encode for the lambda light chain of immunoglobulin are present on chromosome 22. The lambda light chain gene locus on chromosome 22 also contains the variable (V) and joining (J) gene segments, as well as the constant (C) gene segment. The arrangement of these gene segments results in the expression of a functional lambda light chain.

10-b) 12
In mice, the genes that encode for the heavy chain of immunoglobulin are present on chromosome 12. The heavy chain gene cluster on mouse chromosome 12 contains multiple gene segments that undergo V(D)J recombination to generate the diverse repertoire of antibody variable regions.

11-b) AT-rich nucleotide sequence
The correct answer is b) AT-rich nucleotide sequence. The RSS consists of a conserved heptamer sequence (5'-CACAGTG-3') and nonamer sequence (5'-ACAAAAACC-3') that flank a stretch of DNA that is either 12 base pairs (12-RSS) or 23 base pairs (23-RSS) in length. The spacer region between the heptamer and nonamer sequences is AT-rich, which allows for the formation of a DNA hairpin during the recombination process.

12-a) They catalyze the cleavage of one strand of the DNA

13-b) M1 and M2 exons
14-b) IgM and IgD 
15-a) Assembly of two heavy chains (HH) followed by light chain (LL) and H2L2 
16-c) Assembly of two heavy chains (HH) followed by light chain H2L and H2L2 
17-d) Oct1
18-b) Recombinant DNA technology
19- d) All of the above
20-b) The genes from one parent are expressed in a cell


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