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B-Cells - Coggle Diagram
B-Cells
Development
Commitment
Hemopoietic stem cells commit to B-cell development
Pro-B-Cells bind to Mesenchymal cells that release growth factors
Stages of Development
Antigen Independent Steps
Bone marrow stem cell commitment to B-cell development
Early Pro-B-Cells
Undergoes Heavy chain D-J recombination
2 attempts at successful recombination
Failure leads to Apoptosis (~50%)
Success leads to late development
Late Pro-B-cells
V-DJ recombination of the heavy chain
Two attempts
Failure = apoptosis
Success
Binding with a surrogate light chain to form Pre-BCR
Pre-BCR
Express BCR on surface
Pre-BCR testing (checkpoint #1)
Apoptosis
Success
Antigen Dependent Steps
Undergoes Light chain recombination (kappa or lambda)
Pre-B-cells w/ functional L chains express complete BCR
First round of Negative selection (Checkpoint #2)
Non-functional or self- reactive
Apoptosis
Functional BCR
Survival and proliferation into immature/transitional B-cell
IgM is Expressed and V-J is rearranged
Transitional B-cells express completed BCR
BCRs go through negative selection (checkpoint #3)
High affinity = Apoptosis
Develop into mature B-cells and exit Bone marrow
Migrates to Secondary lymphoid organs to undergo peripheral tolerance
Activation/mediated immunity
The Germinal Centre
Comprised of multiple layers each with different functions
The Dark zone
Rapidly proliferating B-cells
Somatic hypermutation
Densly packed
The Light zone
Storage of Follicular T-Cell helpers
Reactivity test with B-cells
Failure sends B-cells back to Dark zone
Slow proliferating B-cells
Lose of CXCR4 but simultaneous gain of CXCR5
The Mantle
Peripheral edge of the follicle
Contains resting B-cells
Main goal is to optimize the antibodies to be as efficient as possible vis Somatic hypermutation and Affinity maturation
Linked Recognition
Antigen Presentation by FDC
Uptake of antigens and presentation by FDC to B-cells in the follicle of the germinal center
FDC = Follicular Dendritic cells (not actually dendritic cells
Follicular TH cell aid in the Germinal Center
Provide co-stimulatory signals to B-cells that have interacted with FDC
Facilitates activation and differentiation
Differentiation can be to the production of plasma blasts or Germinal Center B-cell
B-cell activation can be either Thymus dependent or independent and requires 2 activation signals
Thymus Dependent
2nd Signal: NF-Kb pathway
1st signal: Ras/MAPK
Thymus Independent
Thymus Independent molecules induce IgM molecules to mount first response
IgM is able to class switch later on
2nd signal: MyD88, IKky
1st Signal: Ras/MAPK
Types of Immunoglobulins
IgE
IgA
IgG
IgD
IgM