B Cells Flashcards
Describe the mechanism for immunoglobulin diversity (shared by B cell Ig receptors and TCRs)
Constant region coded for by contant region DNA
Variable region coded by 3 separate genes: Variable, Diversity, Joining
Random Ig gene rearrangement results in a broad diversity of Ig
What is the effect on B cell development of mutations of the B Cell receptor (or accessory molecules for surface Ig expression)
Failure of B cell development at the Pre-B/Pro-B stage
B cells need receptors to develop
BAFF (B cell activating factor) also essential for B cell development and arrest –> failure
Why is it ineffective to vaccinate neonates?
B-1 B cells predominate in the foetus/neonate and decrease in the periphery with age
found mainly in the pleural/peritoneal cavity and spleen
Constitutively produce Ig (no stimulation required) with limited diversity
Respond to carbohydrate and T-independent antigen, respond poorly to protein, limited somatic mutation and isotype switching, INDUCE NO/POOR MEMORY RESPONSE
Describe the innate and specific immune function of B-1 B cells
Innate: secrete large amounts of IgM that is polyspecific spontaneously
Specific: produce majority of secretory IgA, differentiate into IgA secreting plasma cells without T cell help
What are the features of a naive B cell
- surface Ab
- surface receptor
- lifespan
- activation
- affinity for Ab
- co-stim molecules
- location
What are the features of a naive B cell
- surface Ab: IgM, IgD
- surface receptor: CD5-/lo, CD23+, CD27-
- lifespan: short
- activation: higher threshold than mature
- affinity for Ab: low
- co-stim molecules: not expressed
- location: follicle
What are the features of a memory B cell
- surface Ab
- surface receptor
- lifespan
- activation
- affinity for Ab
- co-stim molecules
- location
What are the features of a memory B cell
- surface Ab: IgM-only or IgM, IgD, IgG, IgA, IgE
- surface receptor: CD5-, CD23+/-, CD27+
- lifespan: long and larger
- activation: lower threshold than naive
- affinity for Ab: higher
- co-stim molecules: express CD80, CD86
- location: marginal zones
What is thymus independent antigen?
an antibody response is generated without T cell response
Type 1: an intrinsic ability to induce B cell proliferation (poor isotype switching, affinity maturation, memory) eg LPS
Type 2: highly repeptitive molecules extensively cross link the BcR and activate the B cell eg bacterial capsular polysaccharides, although not required, cytokines from T cells increase efficiency
What is the importance of thymus independent immune response?
Allows rapid production of Ig without the requirement for antigen processing
It is deificient in neonates and splenectomised patients
What is thymus dependent antigen?
Protein antigen- poor response in thymectomised mice (no secondary response, no memory B cells)
Response of B cell to most antigen requires binding of antigen to BCR, interaction with antigen specific activated helper T cells (CD40 on B cell to CD40 ligand on T cell)
Evokes primary and secondary immune responses, and isotype switching
GENERATES MEMORY
Primary immune response predominated by?
Naive B cell–> activated B cell
produces mostly IgM (peak at 7-10days), some IgG
Generates plasma cells (located in bone marrow)
smaller peak response
lower affinity, response more variable
induced by all immunogens (adjuvants for protein immunisation required)
Secondary immune response predominated by?
Plasma cell–> memory B cell
Antibody secreting cell produces mostly IgG (peak at 3-5 days), some IgM
larger peak response and much higher
higher affinity 2 to affinity maturation
protein antigen and low dose (adjuvant not necessary)
What cells are predominantly located in the follicle of the lypmh node?
B cells
What cells are predominantly found in the periarteriolar lymphoid sheath of the lymph node?
T cells
What happens in the germinal centres to B cells?
Activated B cells travel to the germinal centre where they undergo clonal expansion and somatic hypermutation, high affinity clones receive a survival signal from the follicular dendritic cells, low or auto affinity clones do not receive the survival signal and undergo cell death (B cell Hunger Games)
High affinity cells then differentiate into memory or plasma cells, plasma cells travel to the bone marrow where they require constant messaging to maintain survival (need for booster vaccinations)
What are the molecular requirements for development of a naive B cell into a germinal centre B cell (relevant to PID)
CD40 CD40L ICOS NEMO SH2D1A (SAP)
