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

2. Kindt • Goldsby • Osborne
Kuby IMMUNOLOGY
Sixth Edition
Chapter 11
B-Cell Generation, Activation,
and Differentiation
Copyright © 2007 by W. H. Freeman and Company

3. 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

4. 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)

6. B cell Activation Membrane bound antibody have short cytoplasmic tails
Too short to generate signal by associating with tyrosine kinases and G proteins
Membrane Ig must be associated with B-cell receptor
Ig-α/Ig-β

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

10. TH cells play essential role in B cell repsonses

11. TEM of interaction between B cell and T cell

12. Humoral Response – Primary vs Secondary

14. Hapten-carrier conjugates
Hapten – low molecular weight molecule that won’t itself induce a humoral response
Must be coupled to suitable carrier

16. In vivo sites for induction of humoral responses
Blood-bourne antigen is filtered by spleen
Antigen from tissue spaces filtered by lymph nodes
Antigen either enters alone or with antigen-transporting cells
Langerhans cells
Dendritic cells
Encounters antigen-presenting cells
Macrophages
Follicular dendritic in follicles and germinal centers

18. T cells are green and B cells are red

19. 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

20. 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

21. 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

22. 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