B Cell Response

1. B Cell Response

2. The basic process of humoral immune response Plasma cell Antibody Antigen recognition B cell activation Memory B cell Initiate a B cell response in the presence of Th cell TD-Ag Two types of antigens Initiate a B cell response in the absence of Th cell TI-Ag

3. I. B cell response to TD-Ag TD-Ag: composed of T and B cell epitopes T cell epitope (peptide) + MHC class II Bind to TCR B cell epitope Bind to BCR

4. Antigen Recognitionby BCR Antigens recognized by BCR can be proteins, polysaccharides, nucleic acids, lipids, or small compounds. BCR recognizes both linear and conformational epitopes. They do not need not to be processed by APCs.

5. Signal Transduction following BCR Engagement

6. Signal Transduction following BCR Engagement

7. Signaling by B cell-co receptor The B cell co-receptor is a complex of three proteins: CD19, CD21 and CD81. Complement-coated antigens cross-link BCR and the co-receptor. The long cytoplasmic tail of CD19 is then phosphorylated and serve as docking sites for a large number of signal transducers, thereby amplifying the BCR signal.

8. No Th B anergy Signal 1 IFN-g , IL-4, IL-5 B Th activation Signal 1 Signal 2 Dual-signal Model for B Cell Activation Signal 1 from BCR-antigen interaction Signal 2 from interaction between CD40 on B cells and CD40L on activated T cells

9. Interaction of T-B Cellsin B Cell Responses Th cell begins to express CD40L Antigen crosslinks mIg CD40L-CD40 interactions provide signal ② generate signal ① Th cell secreted cytokines increased expression of MHC II and B7 activate Th cell

10. Germinal Center Reaction The activated B proliferates extensively and forms a germinal center.

11. Important events in germinal center • Somatic hypermuatation

12. Follicular dendritic cells… not an APC! • The follicular dendritic cells do not have MHC-II and B7 • Expressing high levels of Fc receptor

13. Selection of mutated clones Affinity maturation: The affinity of the antibodies increases progressively

14. Important events in germinal center • Antibodyclass switching The antibodies produced in primary response are mainly IgM. But they switch to other classes (IgG, IgA and IgE) late in the response or in secondary response.

15. Cytokines and class switching

16. Generation of plasma and memory cells

17. Characteristics of plasma cells Specialized Ab producing facility 1000 molecules/sec Increased transcription Shut-off of production of other proteins

18. Comparison of naïve and memory B cells

20. Log Plateau Decline Lag A b T i t e r Ag D a y s A f t e r I m m u n i z a t i o n Kinetics of the Ab Response Lag: naive B cells undergo clonal selection, expansion, and differentiation. Log: a logarithmic increase in serum antibody level Plateau: reaches a peak, plateaus for a variable time

21. The secondary response • Activation of memory cells by antigen results in a secondary antibody response that can be distinguished from the primary response in several ways.

22. Primary vs secondary response The secondary response • has a shorter lag period • reaches a greater magnitude and lasts longer • Ab with a higher affinity for the Ag, and isotypes other than IgM predominate

23. Primary vs secondary response

24. II. B cell response to TI-Ag • Two types of TI-Ag: TI-1 antigen and TI-2 antigen • different mechanistic properties • B cells response are different

25. TI-1 antigen • Typical TI-1 antigens are LPS （bacterial cell wall component） • Induce activation of many B cells, both specific and nonspecific. No: class switching, affinity maturation and memory Low affinity IgM

26. TI-2 antigen • Polysaccharides from bacterial cell walls • Polymeric protein structures such as bacterial flagella

27. What to remember • Primary vs secondary responses • T cell help for B cell response • Critical events in GC