Lecture 4: B-cell development Flashcards
B-cell development
1: Pro-B Cell (Stem cell)
2. Pre-B cell receptor (Pre-BCR)
3. Immature B cell
4. Native Mature B cell
5. Plasma Cell and memory cells
Pro-B cell (stem cell)
H-chain gene rearrangement: D-J join and then V-DJ; no markers/antibody markers
Pre-B cell receptor (Pre-BCR)
- surrogate L chain moves to surface
- μ heavy chain + surrogate light chain
- L-chain rearrangment triggered (kappa or lambda genes rearrange and replace the products of the surrogate light chain –> V-J
Immature B cell
IgM on surface; negative selection leads to central tolerance (auto/self-reactive B cells eliminated) –> immature b cells exit bone marrow and enter periphery
Native Mature
- express IgM and IgD on their surface once they leave the bone marrow (naive bc they have not yet encountered Ag)
- enter secondary lymphoid organs where they are now active, and become associated with foreign antigens and differentiate again into plasma cell and memory cells.
Requirements for B-cell maturation?
- Recombinases (RAG1 and RAG2)
- Terminal deoxytransferase (TDT)
- Bruton’s Tyrosine Kinase
- Igα and Igβ
- Transcription factors (stromal cells secrete IL7)
Terminal deoxytransferase (TDT)
a polymerase like enzyme that can add nucleotides without a template, causing a shift in reading frame and therefore proteins with altered specificity –> junctional diversity
Recombinases (RAG1 and RAG2)
molecules that cut into DNA and enable rearrangement of gene segments
Bruton’s Tyrosine Kinase
intracellular protein that mediates signal transduction during Bcell development; without it B cell development does not occur and B cell dies
Igα and Igβ
heterodimer that mediates signal transduction after the B cell binds with antigen to become activated
Examples of primary and secondary lymphoid organs
primary: bone marrow and thymus
secondary: lymph nodes, spleen, MALT
Red pulp
- Filtering fxn
- Macrophages and dendritic cells
- Phagocytosis: innate immune function; macs engulf via PAMPs/PRRs
- Opsonization
Opsonization
- Antibody mediated immune function; bacteria that are encapsulated hide from phagocytes, so that the body needs another way to eradicate them.
- Best way is to coat the capsule with Ab and complement components: C3B –> now the bacteria can be recognized by specific receptors on the macrophage surface
Primary fxn of the spleen
Phagocytosis of blood-borne microbes (red pulp) and antibody production (white pulp)
Routes of antigen entry
Inhalation
Ingestion
Sexual contact
MALT
What signals are required to activate a naive B-cell?
Signal 1: Antigen binding
-APC: internalizes Ag, processes, and presents w/ MHCII
Signal 2: T-cell signal (TH2); costimulatory [CD40L (on T-Cell) + IL4)
-2nd signal delievered by helper T-cells; ensures peripheral tolerance (tolerant to all self-antigens)
-If B cell internalizes self Ag and presents it on surface, T cell will not recognize it and B cell will become Anergic
-Helper T cell recognizes specific antigen w/ MHCII and it delivers a 2nd signal in the form of CD40 ligand interacting w/ CD40 that’s on the surface of the B cell and the secretion of IL-4
Linked recognition
B cells are activated by T-cells that recognize the same antigen (any epitope)
Antigen
Any substance that can bind with Ab
Immunogen
Any substance that can bind with Ab and elicit an immune response (stimulate B/T cell activation)
Hapten
Small molecule that can bind with Ab but does not elicit an Bcell immune response bc a hapten is too small to associate w/ MHC (therefore, cannot induce production of Ab)
Adjuvants
- Substances that increase the immunogenicity of substances mixed with it
- Not carriers
- They can 1) prolong the life of the immunogen within the body and mimic bacterial substances and enhance by stimulating macrophages and 2) getting early inflammatory process going
- added to vaccines
- ex: Old DPT (diphtheria), pertussis (bacterial cell components stimulate innate immune response), and tetanus vaccines
