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22 Cards in this Set
- Front
- Back
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Describe how allelic exclusion causes B cells to be monospecific ie. specific for only one antigen
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Allelic exclusion is that B cells only express 1 heavy chain allele
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Diagram the BCR and name its components
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1) Heavy chain
2) light chain 3) Ig B 4) Ig alpha 5) transmembrane domain |
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List and describe the effects of antigen on Ig expression?
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1) somatic hypermutation - affinity maturation
2) alternations in RNA processing can yield change from membrane Ig to secreted antibody 3) isotype switching |
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How is somatic hypermutation related to affinity maturation?
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mutations caused by somatic hypermutations occur preferentially in regions where Ig and antigen interact this then causes affinity maturation
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What are the effects of isotype switching on the heavy chain locus?
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DNA rearrangement occurs when cytosine deaminase moves the VDJ over to another heavy chain constant region
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What are the differences in genomic organization on protein structure?
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structural differences are responsible for functional differences
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Describe the structural differences among the isotypes?
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-different physical properties
-different physical abilities such as serum level, diffusion into extravascular sites, transport across placenta, transport across epithelium -different functional abilities such as neutralization, opsonization, senitization of cytotoxic cells, sensitization of mast cells, activation of complement |
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What is the difference in the secreted vs membrane Ig DNA?
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-membrane Ig has extracellular, transmembrane and cytoplasmic region
-membrane region is longer -secreted form only has short tail |
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What is the purpose of Igbeta and Ig alpha
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necessary for mIg expression and for signal transduction
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What is light chain isotype exclusion?
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B cells only express one allele of light chain - either kappa or lambda
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What property is responsible for B cell monospecificity?
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allelic exclusion
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Do all isotypes have membrane and secreted forms?
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all except for IgD which is only on the membrane
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What enzymes are responsible for somatic hypermutation?
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cytosine deaminase, UNG, APE1
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What does cytosine deaminase do?
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attacks pyrimidine ring of cytosine in single stranded DNA and converts C to U
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What is the biochemical steps of somatic hypermutation?
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-transcription occurs so that local single stranded DNA is formed
-B cell AID attacks cytidine in ssDNA to produce uridine -UNG removes uracle to form apyrimidic residue -APE1 excises ribose to form ss nick in DNA -ss nick in DNA is repaired |
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What is the first antibody produced?
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IgM
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What are the two forms of IgM?
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monomeric membrane IgM
secreted pentamer IgM held together by protein J |
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What is the name of the protein that holds IgM secreted pentamer together?
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J
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What causes the isotype switching?
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recombination between S regions that are 5' to every C except for C delta
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What are the two Igs that form multimers?
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IgA and IgM
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What are the 7 changes that Ig undergoes during the life of a B cell?
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1) V region assembles from different fragments via somatic recombination
2) junctional diversity 3)transcriptional control elements - promoter and enhancer brought together as V region is put together 4) transcription activated with coexpression of surface IgM and IgD 5)synthesis of membrane Ig changes to secreted Ig 6) somatic hypermutation 7) isotype switching |
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What are the changes that Ig undergoes that are reversible and regulated?
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1) transcription activated when IgM and IgD are expressed on surface
2)transition from membrane Ig to secreted Ig |
