1. B Cells Flashcards
Immunoglobulin (Ig): Key Features
2 heavy chains
2 light chains
disulphide bonds
heavy chain
3 constant domains = CH1, CH2, CH3
1 variable domain = VH
light chain
1 constant domain = CL1
1 variable domain = VL
IgM
secreted as a pentamer
held together by a J chain
10 binding sites
efficient at agglutinating bacteria
1st antibody produced in an infection
found on B cell as an antigen receptor
IgG
4 subclasses: IgG1, IgG2, IgG3 and IgG4
most prevalent antibodies in serum
only antibodies that can cross the placenta
IgA
secreted as a dimer
held together by a J chain
contains a “secretory component” (SC)
protects the mucosa
secreted locally by plasma cells e.g. in saliva, milk and tears
IgD
present in low levels in the serum
B cell antigen receptor
IgE
involved in inflammation
protection from parasitic worms
low serum levels
binds to IgE receptors on a mast cell associated with antibody-mediated allergy
Isotypes
present in all healthy individuals – Ig classes and subclasses
Allotypes
genetically restricted variation within CH region
Idiotypes
individual antigenic characteristics of a given antibody
based on its variable region
Four main mechanisms for Antibody Diversity
- Combinational diversity 2. Junctional diversity 3. Heavy/light chain pairings 4. Somatic hypermutation
2 types of light chains
- Kappa 2. Lambda
Junctional diversity
RAG enzymes cleave DNA at random positions along the region
Random nucleotides are added (or deleted) for extra variability
This somatically recombined DNA is then processed
Transcription and Splicing
somatically recombined DNA is transcribed into pre mRNA
introns are spliced out, combining the V,J and C regions
translated into the light chain in the ER
Class Switching
Somatic recombination at Switch (S) regions replace IgM
Somatic hypermutation
AID converts cytosine to uracil
Hyper-mutation occurs when cells try to fix the error
B cells producing antibodies with higher affinity for antigen are selected to survive
Defect in somatic recombination
Omenn Syndrome
Curable by bone marrow transplantation
B-cell development
B cell precursor rearranges its immunoglobulin genes
Generation of B cell receptors in the bone marrow
Negative selection in the bone marrow
B cell is activated when foreign antigen binds
B cells migrate to the peripheral lymphoid organs
give rise to plasma cells and memory cells
Antibody secretion
B cell function
secretes antibodies
B-cell receptor (antibody) signalling
IgM or IgD
Kinase activation (tyr phosphorylation)
Ca2+ release
TF activation
Immunological memory
memory cells
Re-exposure of antigen = more rapid response
