1. Chapter 11
B-Cell Generation, 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. Development of B cells
In many vertebrates, including humans and mice, B cells generate in bone marrow
Antigen-independent phase
Ig-gene rearrangement to create antigen-specificity
Immature B cell bearing IgM on membrane leaves bone marrow
Matures to express both IgM and IgD with single antigen specificity
NAÏVE B cells – have not encountered antigen
Encounter antigen in secondary lymphoid tissue
Differentiate into plasma cells and memory cells
Class switching

5. Bone marrow Pro-B cell → precursor B cell
Stromal cell in bone marrow secrete IL-7 that help development into immature B cells

6. Pro-B Cell Pre-B cell Immature B cell Heavy chain rearrangement
Light chain rearrangement
Immature B cell
Is now committed to antigenic specificity and produces IgM
B cell not fully functional, must first express both IgM AND IgD on membrane

9. In mice, 90% of B cells produced everyday die without ever leaving bone marrow
Negative selection due to cells that express auto-antibodies against self antigen in the marrow

11. B cell Activation Thymus-dependent (TD) antigens
B cell required direct contact with TH cell
Thymus-independent antigens (TI)
These antigens activate B cells by different means
Type I (TI-1) – lipopolysaccharide
Type 2 (TI-2) – highly repititous molecules (bacterial flagella)

13. 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

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

17. TH cells play essential role in B cell repsonses

18. TEM of interaction between B cell and T cell

19. Humoral Response – Primary vs Secondary

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

23. 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

25. T cells are green and B cells are red

26. 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

27. 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

28. 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

29. 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