Lecture 4: B-cell development

Question 1

B-cell development

Answer 1

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

Question 2

Pro-B cell (stem cell)

Answer 2

H-chain gene rearrangement: D-J join and then V-DJ; no markers/antibody markers

Question 3

Pre-B cell receptor (Pre-BCR)

Answer 3

• 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

Question 4

Immature B cell

Answer 4

IgM on surface; negative selection leads to central tolerance (auto/self-reactive B cells eliminated) –> immature b cells exit bone marrow and enter periphery

Question 5

Native Mature

Answer 5

• 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.

Question 6

Requirements for B-cell maturation?

Answer 6

1. Recombinases (RAG1 and RAG2)
2. Terminal deoxytransferase (TDT)
3. Bruton’s Tyrosine Kinase
4. Igα and Igβ
5. Transcription factors (stromal cells secrete IL7)

Question 7

Terminal deoxytransferase (TDT)

Answer 7

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

Question 8

Recombinases (RAG1 and RAG2)

Answer 8

molecules that cut into DNA and enable rearrangement of gene segments

Question 9

Bruton’s Tyrosine Kinase

Answer 9

intracellular protein that mediates signal transduction during Bcell development; without it B cell development does not occur and B cell dies

Question 10

Igα and Igβ

Answer 10

heterodimer that mediates signal transduction after the B cell binds with antigen to become activated

Question 11

Examples of primary and secondary lymphoid organs

Answer 11

primary: bone marrow and thymus
secondary: lymph nodes, spleen, MALT

Question 12

Red pulp

Answer 12

• Filtering fxn
• Macrophages and dendritic cells
• Phagocytosis: innate immune function; macs engulf via PAMPs/PRRs
• Opsonization

Question 13

Opsonization

Answer 13

• 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

Question 14

Primary fxn of the spleen

Answer 14

Phagocytosis of blood-borne microbes (red pulp) and antibody production (white pulp)

Question 15

Routes of antigen entry

Answer 15

Inhalation
Ingestion
Sexual contact
MALT

Question 16

What signals are required to activate a naive B-cell?

Answer 16

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

Question 17

Linked recognition

Answer 17

B cells are activated by T-cells that recognize the same antigen (any epitope)

Question 18

Antigen

Answer 18

Any substance that can bind with Ab

Question 19

Immunogen

Answer 19

Any substance that can bind with Ab and elicit an immune response (stimulate B/T cell activation)

Question 20

Hapten

Answer 20

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)

Question 21

Adjuvants

Answer 21

• 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