1. Chapter 12 B-Cell Activation and Differentiation Dr. Capers
Immunology

2. B cell activation B cell encounters specific antigen
B cell presents to T helper cell
Cytokines are released for full B cell activation
Proliferation, some of the B cells become plasma cells
Some of the B cell clones move to germinal centers of lymph nodes, somatic hypermutation can occur
Class switching occurs

3. The tiny region of the antigen that BCR actually binds to is called its “epitope”.
The epitope will be the part of that protein (usually 6 – 12 amino acids) to which the BCR receptor binds.

4. When the BCR recognizes the epitope, for which it is matched, it must signal this recognition to the nucleus of the B cell, where genes involved in activating the B cell can be turned on or off.

5. B cell Activation Thymus-dependent (TD) antigens
B cell required direct contact with TH cell
B-2 B cells, majority of B cells
Thymus-independent antigens (TI)
These antigens activate B cells by pattern recognition receptors (bacteria that might be in high amount)
Type I (TI-1) – lipopolysaccharide
Type 2 (TI-2) – highly repititous molecules (bacterial flagella)

7. B cell Activation Membrane bound antibody have short cytoplasmic tails
Too short to generate signal by associating with tyrosine kinases and G proteins

8. Membrane Ig must be associated with B-cell receptor
So that the external part of the BCR can signal what it has seen, B cell are equipped with two accessory proteins
Membrane Ig must be associated with B-cell receptor
Ig-α/Ig-β

9. ITAMS
ITAMs are important for signal transduction in immune cells. An ITAM is a specific sequence of amino acids occurring twice in close succession in the intracellular tail of a receptor

10. They are found in the tails of important cell signaling molecules such as the CD3 and ζ-chains of the T cell receptor complex, the CD79-alpha and -beta chains of the B cell receptor complex, and certain Fc receptors.

11. The tyrosine residues within these motifs become phosphorylated following interaction of the receptor molecules with their ligands and form docking sites for other proteins involved in the signaling pathways of the cell

14. ITIM (immunoreceptor tyrosine inhibitory motif)
Associated with CD22
Functions to deactivate B cells – negative regulation
Important in preventing autoimmunity

15. TH cells play essential role in B cell repsonses

16. Remember: B cells can be t-cell independent or dependent!

17. TEM of interaction between B cell and T cell

18. Humoral Response – Primary vs Secondary

20. Hapten-carrier conjugates
Hapten – low molecular weight molecule that can elicit an immune response only when attached to a large carrier such as a protein.

22. In vivo sites for induction of humoral responses
Bloodborne antigen is filtered by spleen
Antigen from tissue spaces filtered by lymph nodes
Antigen either enters alone or with antigen-transporting cells
Langerhans cells (antigen-presenting immune cells) of the skin and mucosa
Dendritic cells
Encounters antigen-presenting cells
Macrophages
Follicular dendritic in follicles and germinal centers

24. T cells are green and B cells are red

25. Germinal centers arise within 7-10 days after initial exposure to thymus-dependent antigen in lymph node
3 events in germinal centers
Affinity maturation
Result of somatic hypermutation
Class switching
Formation of plasma and memory B cells

26. Cellular events in germinal centers
Dendritic cell presents antigen
to developing B cells to see
which B cells are producing
antibody with high-affinity
for that antigen

27. Class Switching
Dependent on cytokines to switch from IgM to other isotype
Thymus-dependent antigens
Interaction of CD40 on B cell and CD40L on T cell
X-linked hyper-M syndrome
TH cells don’t express CD40L, patients only produce IgM
No memory cell populations, no germinal centers

28. Regulation
Humoral and cell-mediated branches must be heavily regulated
Cytokines play important role
Antigenic competition
Previous encounter with antigen can render animal tolerant or may result in formation of memory cells
Presence of antibody can suppress response to antigen
Some vaccines are given to babies after maternal IgG (that was transferred across placenta) has left system
Vaccination before this will prevent proper response and development of long-lasting memory cells