B Cells Flashcards
How is the BcR bound to the cell?
What are antibodies?
What is the general shape of BcRs/Abs?
Via transmebrane protein
Antibodies are secreted proteins often looking identical to BcRs but with no transmembrane region.
Y shaped.
Briefly describe the Y shaped antibody.
4 polypeptide chains: 2 light and 2 heavy
Disulfide bonds hold heterodimers together
Variable regions, hinge domain, and Fc region
List the five main isotypes of antibodies in mammals. Give a brief description of each.
IgA: In mucosal areas. Prevents colonization by pathogens
IgD: Ag receptor on B cells. Cell activation.
IgE: Binds to allergens and triggers histamine release. Also protects against parasitic worms.
IgG: provides majority of Ab based immunity. Only Ab capable of crossing placenta to give passive immunity.
IgM: On surface of B cells. Eliminates pathogens in early stages of humoral immunity with sufficient IgG.
What is humoral immunity mediated by?
B cells
Briefly describe the serotype conversion of Abs during infection.
IgM proceeds IgG. IgG persists months to years. IgG levels are boosted after secondary infection.
Describe in brief the location and function of IgA.
AgA is secreted at mucosal surfaces. plgR is on the basolateral side of columnar epithelials and binds the J chain of IgA and IgM. Secretory component protects Abs from acid/proteases.
IgA is used in immune exclusion, intracellular neutralization, and Ag excretion.
how do B cells morph their Ig to become more specific?
What does this process require?
VDJ recombination
RAG1/2 complex
What drives the diversity of antibodies further?
Multiple gene segments P nucleotide addition exonuclease trimming Non-template N nucleotide addition Combinatorial diversity Somatic hypermutation
Define the following: Multiple gene segments P nucleotide addition Exonuclease trimming Non-template N nucleotide addition Combinatorial diversity Somatic hypermutation
VDJ segment recombination
Adds short palindromic sequence at the joint
loss of nucleotides at junction
Up to 20 extra nucleotides can be added at the joints of heavy chain genes
Heavy chain can combine with different light chains and vice versa
Through AID enzyme and DNA repair the variable regions are mutated in the loci that code for them.
Briefly discuss and define class switch recombination in B cells
Process by which Ig heavy chain locus constant region is changed but the variable region remains the same (aka isotype switching).
This does not alter Ag specificity.
Is central to maturation of the Ab response
Crucially requires AID
How do T cells involve themselves in B cell isotype switching?
Each subtype of T helper cells secrete different cytokines which promote the isotype switching. Cytokines in mucosal lymphoid tissue promote switching to IgA.
Describe the B cell clonal selection hypothesis
Each B cell has a single type of BcR. Each one will create a clone of itself with the same Ag receptor as the original. Only the activated B cells can clonally expand to become plasma or memory cells.
Describe initial B cell Ag recognition.
Initial interactions induce a clustering of BcRs and their Ags. Ag bound BcR move into lipid rafts which allow association of BcR signalling molecules and an activation signal. B cell membrane spreads over entire target before contracting back and BcR clustering induces internalization and Ag presentation by B cell.
What do monovalent Ag cause in B cells? Multivalent?
Mono: causes conformation change in BcR to allow clustering.
Multi: also promote BcR clustering
Describe T cell dependent B cell responses.
B cells bind to Ag via BcR. This provides a survival signal, some Ag is internalized, processed, and presented on MHC II. In SLOs, interaction with Th cells provides co-stim and cytokines for differentiation and memory cell production.
B cells express CCR7 after Ag processing and move into T cell zone to encounter Ag specific T cells. B cells then down regulate CCR7 and leave T cell areas for follicles.
