Question

Case Study: As a member of a research team studying a tribe found in a remote region of New Guinea, you make the astonishing discovery that they have only two V genes for the L chain and three V genes for the H chain of immunoglobulins. Nevertheless, they seem healthy and able to resist the diversity of pathogenic organisms endemic to the area. Suggest how this might be accomplished 1. The DNA for an H chain in a B cell making IgG i2 antibody for diphtheria toxoid has the following structure: 5-V-Ds J2 Се-Су- B-cell DNA? C& Car-3 How many individual rearrangements were required to go from the embryonic DNA to this A) 1 B) 2 C) 3 D)4 E) none 2. If you had 50 V, 20 D, and 6 J regions able to code for a heavy chain, and 40 V and 5 J region genes able to code for a light chain, you could have a maximum repertoire of A) 76+ 45 121 antibody specificities B) 76 x 45 3420 specificities C) (40 x 5)+ (50 x 20 x 6) 6200 specificities F) none of these D) (40 x 5) x (50 x 20 x 6) = 1,200,000 specificities E) more than 1,200,000 specificities 3. The antigen specificity of a particular B cel A) is induced by interaction with antigen. B) is determined only by the L-chain sequence. C) is determined by H + L-chain variable region sequences. D) changes after isotype switching E) is determined by the heavy-chain constant region. F) none of these 4. If you could analyze, at the molecular level, a plasma cell making IgA antibody, you would find all f the folowing except A) a DNA sequence for V, D, and J genes translocated near the Ca DNA exon B) mRNA specific for either K or λ light chains C) a DNA sequence coding for the T-cell receptor for antigen. . D) mRNA specific for u chains E) mRNA specific for J chains ability of a single B cell to express both lgM and IgD molecules on its surface at the same time is made possible by A) use of genes from both parental chromosomes B) isotype switching C) simultaneous recognition of two distinct antigens. D) selective RNA splicing. E) allelic exclusion.

Answer 1

Solution:

1. The correct option is (C) i.e. 3

Reason - There are three individual rearrangements required as the first rearrangement occurs from D₅ to J_2. It is followed by the second rearrangement i.e. V₁₇  to D₅J_2. By the use of V₁₇D₅J₂ , the synthesis of antibodies IgM and IgD molecules occur. The last reaarangement is the class switch of V₁₇ D₅ J₂ C_µ C_δ to V₁₇ D₅ J₂ C_γ2 which leads to the synthesis of IgG₂ molecules.

2. The correct option is (E) i.e. more than 1,200,000 specificities

Reason - There will be imprecise recombinations of VJ or VDJ segments, insertional diversity, and somatic hypermutation which leads to production of many more specifities even more than 1,200,000.

3. The correct option is (C) i.e. determined by H+L-chain variable region sequences

Reason - Heavy and long chain variable region sequences determine the antigen specificity in the B-cell. No antigen, isotype switching or either of L or H chain works for this antigen specifity. It is only determined by combination of both heavy and short chains.

4. The correct option is (D) i.e. mRNA specific to µ chains

Reason -  As a result of the rearrangement of the VDJ to Cα in the IgA producing cell, the Cµ gene will be deleted. The other DNA sequences and mRNA species will also be found in the cell.

5. The correct option is (D) i.e. selective RNA splicing

Reason - Alternate splicing of the primary RNA transcript made it possible to synthesise the IgM and IgD antibodies along with the expression.