Two proteins, Rag-1 and Rag-2, catalyze VDJ recombination. What is the likely outcome of a deletion of the Rag genes?  

A.  mild susceptibility to infection due to T cell defects
B.  increased antibody diversity from B cells
C.  severe combined immunodeficiency (SCID) of both B and T cells
D.  increased resistance to infection due to enhanced B and T cell function


Clarify Question
What is the key concept addressed by the question?
What type of thinking is required?
 
Gather Content
What do you already know about the VDJ segments? What other information is related to the question?
 
Choose Answer
Given what you now know, what information is most likely to produce the correct answer?

Reflect on Process
Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?


C.  severe combined immunodeficiency (SCID) of both B and T cells

Clarify Question
What is the key concept addressed by the question?
        · The question is asking about the consequences of the loss of Rag genes.
What type of thinking is required?
        · Apply level:
            o You are being asked to take what you already know and use, or apply, it to the effects of the loss of VDJ recombination on immunoglobulin structure and function.
 
Gather Content
What do you already know about the VDJ segments? What other information is related to the question?
        · Immunoglobulins, or antibodies, have variable regions that recognize specific antigens, as well as constant regions that are similar for different antibodies.
        · Many different combinations are possible for the variable regions.
        · The DNA sequence that codes for the heavy chains of immunoglobulins has approximately 50 V segments, 30 smaller D segments, and 6 smaller J segments.
        · Each segment codes for a different series of amino acids.
        · In the synthesis of a heavy chain of an immunoglobulin, a V, D, and J region are randomly selected and joined together.
        · VDJ recombination leads to thousands of different heavy chain region sequences.
        · Light chains are synthesized in a similar, way except they lack a D segment.
 
Choose Answer
Given what you now know, what information is most likely to produce the correct answer?
        · T cells are not the products of antibodies, so they would be unaffected by this deletion.
        · Antibody diversity would decrease, not increase without these genes, and resistance to infection would decrease as wll.
        · Since VDJ recombination leads to thousands of different heavy chain region sequences, without the recombination, the heavy chains would be quite similar.
        · This would result in immunodeficiency due to lack of antibody diversity.

Reflect on Process
Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?
        · Apply level:
            o Answering this question correctly depended on your ability to use heavy chain formation in a new situation. If you got an incorrect answer, did you remember that heavy chains have three variable components, or that lack of recombination would lead to fewer matches between antibodies and antigens? Did you have trouble extending heavy chain formation to determine the correct answer?

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