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Antibody Allotype Responses to a Genetically Heterogenous Family

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Scenario: Amy and Hooman fell in love, got married, and had a baby named Joe. Joeâ??s grandparents are all alive and are all homozygous at IgH, but share no alleles. Joeâ??s aunts Alison and Negin are Amyâ??s and Hoomanâ??s sisters respectively. Finally, thereâ??s a cat named Tigger. Assume that you purified IgM from Hooman's serum, made Fc fragments, then used them to immunize both grandfathers as well as Aunt Alison and Tigger.

Will the specificity of any of the four anti Hooman ?Fc be exactly the same? Explain.

How will each of the four antisera will react with serum from
each adult family member mentioned (nine if you count the cat).

What proportion of splenic B-cells from each adult family member would be bound by
each of the four antisera?

For each antiserum, what are the odds (%) that it will bind IgM in Joeâ??s serum?

Describe a procedure to modify the Tigger anti-Hooman ?Fc so it would behave the
same as the Alison anti Hooman ?Fc in the above situations.

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Solution Preview

In case the tables do not reproduce well, I have attached a Word file of the entire answer. Please let me know if anything is unclear.

Necessary information:

We can start with the grandparents, who are all homozygous for antibody allotype, but do not share any alleles. We can designate each allele as a, b, c or d, so the genotype of the grandparents for antibody allotypes would be:
Amy's grandfather - aa
Amy's grandmother - bb
Hooman's grandfather - cc
Hoomas's grandmother - dd

As both Amy and Hooman would inherit one allele from each of their parents, their genotypes would be:
Amy - ab
Hooman - cd

Joe's genotype could be any combination of alleles where one is contributed from each parent, the possibilities being as follows:
25% chance - ac
25% chance - ad
25% chance - bc
25% chance - bd

Antibody allotypes are co-dominant, so each individual will express both types of immunoglobulin in their blood. However allelic exclusion in B cells means that each individual B cell expresses only one of the possible allotypes. For example Amy's blood will contain 50% of B cells with the 'a' ...

Solution Summary

This solution deals with the phenomenon of antibody allotypes. When an individual with one allotype is immunized with blood of a different allotype, they make an antibody response against it. The problem addresses which individuals from three generations of a heterogeneous family would make antibody responses against blood from another member of the family, to illustrate both the genetics and the immunology of allotypes.