B Cell Development

Question 1

Stem Cells

Answer 1

• Stem cells commit to B cell development when adhesion molecules VLA-4 on pro B Cell and VCAM-1 on stromal cell interact
• Other CAMs also involved

Question 2

Early Pro B Cell

Answer 2

• C-kit (Pro Bcell receptor) interacts with SCF (stromal cell)
• Heavy chain arrangement

Question 3

Late Pro B Cell

Answer 3

• Begins to express IL-7 Receptor
• Stromal cell secretes IL7 to support development
• Heavy chain arrangement
• failure -> 2nd chromosome. failure -> apoptosis

Question 4

Large Pre B Cell

Answer 4

• After successful heavy-chain rearrangement
• Begins to express mu chain with surrogate light chain
• Pre Bcell receptor on surface sends signal beck to cell indicating heavy chain function is present -> signals to stop heavy chain rearrangement proceed to light chain rearrangement

Question 5

Small Pre B Cell

Answer 5

• Pre B cell receptor is retracted from surface -> mu chain stored in ER
• Begins Vh to DH/JH light chain rearrangement:
• kappa rearranged first, failure -> 2nd chromosome, failure -> lambda rearrangement, failure -> 2nd chromosome, failure -> death

Question 6

Immature B Cell

Answer 6

-Successful H and L chain rearrangement
-Committed to particular Ag specificity
-Express IgM + L chain
-Self Ag Test:
-If does’t react to self Ag → migrates to periphery and matures
-If reacts to self Ag → cross linking of membrane auto antibodies → B cell development arrested → tries L chain rearrangement again → if still self reactive → apoptosis (matures if no longer self reactive)
-

Question 7

Naive Mature B Cell

Answer 7

• Express IgM and low levels of IgD
• Exported from bone marrow to lymphoid organs
• IgD expression increases
• Recirculate between blood and secondary lymphoid tissues

Question 8

B1 Cells

Answer 8

• Arise in embryonic development
• Precedes B2 cell development
• Less diverse H chain rearrangement are less diverse (have low affinity, Polyspecificity)
• Ig production for common bacterial polysaccharides, not protein Ag
• Maintained via self-renewal (risk for cancer), driven by IL 10
• Little or no IgD on surface

Question 9

B cell self activation

Answer 9

-Encounters matching Ag → B cell activation → B cell engulfs/digests Ag → displays Ag on unique MHC → attracts mature helper T cell → T cell secretes cytokines → B cell multiplies/proliferates to plasma cell → secretes Ig → Ig locks onto Ag → Ig + Ag gets cleared by complement cascade

Question 10

B cell activation by APC/T cell

Answer 10

DC cell takes up Ag → travels to lymph node →T cells recognize Ag on Dc → T cells proliferate
→ B cells interact w/ T cells → proliferate to form primary follicle

Question 11

B Cell Proliferation

Answer 11

Plasma Cell:
-Specialized in constitutive synthesis/secretion of Ig
-Does not express cell surface Ig or MHC
-Terminally differentiated and cease to divide
IgG-expressing B cell:
-Isotype switching
(switch from IgM to IgG depending on infection)
High affinity Ig B cell:
-Affinity maturation
(If cant react w Ag as well as it wants to, can backtrack and rearrange genes to try to have better affinity)
-Memory B cell