B Cell Development Flashcards
Where does B cell development begin and end? Selection?
B cell development begins in BM
Mature in periphery (spleen)
Only negative selection
No need for MHC restriction
Charateristics of B cells which are generated from fetal liver
Mainly B1 cells
Ab from B1 bind carbs on pathogens
Never class switch or mature
Always make IgM
Located in body cavities
Self renewing outside of BM
Development in BM
Pre-pro-B cells interact with CXCL12
Pro B cells interact with IL 7
Pre-B cell–> Immature B cell (once it expresses BCR)
Imm B cell leaves BM
Immature B cells circulation and broad what they do once activated
Imm B cells populate secondary organs
Once activated clonally expand to become plasma cells
Home back to BM to make Ab
Some stay in medulla of lymph nodes
Negative Selection in BM
- Clonal deletion of strongly autoreactive cells
- apoptosis
- Central tolerance
- Recptor editing
- reactivation of recombination
- Anergy
- induction of non-responsiveness to stimuli
2 subsets of Imm B cells and Ig
T1 and T2
Differ in gene expression as they progress though the spleen for further maturation
IgM is first expressed on B cells
As they mature more IgD is expressed
Mature primary B2 Cells
AKA
Expression
Goal in life
What do they do
- AKA: Follicular B cells, main B cells
- Express high levels of IgM and IgD
- Circulate btw blood and nodes
- Help respond to Ag with T cell help, make AB
- Only made in BM
- Highly diverse
- Somatic hypermutation
- Variable region: inc rate of mutagenesis, select those with good Ab affinity
- Can class switch
B1 Cells
Biversity
Location
Ig
Actions
- Restricted diversity
- Certain body locations
- DO NOT do somatic hypermutation and DO NOT need T cell help
- Only make IgM, no class switiching
- Only bind carbs on microbes
- Very little/no memory
- Link btw adaptive and innate immunity
- Derived from diff lineage (fetal liver)
- Regenerate outside of BM
Marginal Zone B cells
Location
What can they recognize
Characterized by
- Only in MZ of spleen, white pulp
- Recognize carbs and proteins
- Specialized for bloodborne antigen recognition
- Some dont need T cell help
- Characterized by low levels of IgD and Fc receptor
B and T cell Similarities
- Both originate from BM
- Rearrangement of gene segments to make unique receptors
- random genetic shuffling
- Screening seletion to avoid self-reactivity
- Produce both
- small subsets with discrete functions
- larger general purpose subsets
B and T cell Development Differences
- Location of maturation
- Screening processes
- T cells use +/-
- Specific arrangements and identities of gene segments to build receptors
- Outcomes of Ag receptor stimulation
- B cells require T cell help and make AB
- T cells require presentation and diff into helper and killer
Clonal Selection Hypothesis
- Each B cell has a single unique Ig receptor
- Once it finds an Ag that matches it, it will clonally expand
- Plasma cells pump out AB
- Memory lay low till next time
T cell independent B cell responses to Ag
Generated due to multivalent/polymerized AG
Repetitive polysaccharide can bind tightly and B cell will make AB against
Only can respond with IgM
T dependent B cell response to Ag
- Binding of Ag to BCR induces initial activation and proliferation
- Form germinal center in node/spleen
- Some Ag is internalized and processed
- Presented on MHC II
- Somatic hypermutation allows for stronger binding
- Interact with helper T cells –> differentiation and memory cell
- DC will keep keep AG to prime
Somatic Hypermutation
- Mech to adapt to new Ag, seen during class switching
- Affinity maturation
- SHM diversifies BCR
- Programmed process of mutation affecting variable regions of Ig genes
- Involves Activation Induced Deaminase (AID)
- Basically we are inducing mutations into the genes to randomly produce differnt receptors on the B cells, those that bind the Ag best stay alive
