Immunoglobulin Genetics

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Immunoglobulin Genetics
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Immunoglobulin GeneticsHistory

• Same C region could associate with many V regions
• IgG Ab with different specificities
• Same V region could associate with many C regions
• Same idiotype on IgG and IgM Ab
• V and C regions coded for by separate genes

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Light Chain Gene FamiliesGerm line gene
organization
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Light Chain Gene FamiliesGene rearrangement and
expression
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Heavy Chain Gene FamilyGerm line gene
organization
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Heavy Chain Gene FamilyGene rearrangement and
expression
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Heavy Chain Gene FamilyGene rearrangement and
expression
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Mechanism of DNA Rearrangements

• Recombination signal sequences (RSS)
• Nonmer
• Heptamer
• 1 or 2 turn signals

• Rag-1 and Rag-2

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Order of Ig Gene Expression
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Order of Ig Gene Expression
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Order of Ig Gene Expression Explains

• Why an individual B cell only produces one kind
  of Ig with one kind of light chain
• Why an individual B cell makes only makes
  antibodies of one specificity
• Why there is allelic exclusion

Importance of allelic exclusion??
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Origin of Antibody DiversityHistory

• Definition Diversity (repitoire) is the total
  of all the Ab specificities that an organism is
  capable of expressing
• Theories
• Germ line theory
• Somatic mutation theory

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Origin of Antibody DiversityCurrent concepts

• Multiple V genes

• V-J and V-D-J joining

• Junctional diversity

• N region insertions
• Amino acid sequences not encoded in the germ
  line

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Generation of N region insertions
J
D
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Origin of Antibody DiversityCurrent concepts

• Multiple V genes

• V-J and V-D-J joining

• Junctional diversity

• N region insertions

• Somatic mutation

• Combinatorial association

• Multispecificity

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Generation of Diversity

• Ag independent process

• Clonal selection

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T Cell Antigen Receptor

• Heterodimer of an a and a ß chain
• Gene structure and expression of the a chain is
  analogous to the immunoglobulin light chain
• Gene structure and expression of the ß chain is
  analogous to the immunoglobulin heavy chain
• No somatic mutation in T cells