B lymphocyte-mediate recognition of antigens and the immune response

1. B lymphocyte-mediate recognition of antigens and the immune response

2. Contents • B cell-mediate immune response to T-dependent antigen • B cell-mediate immune response to T-independent antigen • The general rule of humoral immune response

3. Humoral immunity: A immune response mediated by B lymphocyte-secreted antibodies. Its funtion is to neutralize and eliminate the antigens which induced the antibodies.

4. B cell-mediate recognition to antigens B cell-mediate recognition to TI antigens TI-antigen: T-independent antigen This type of antigen can activate B cells without the T cell help, and most of them are bacterial polysaccharides and lipopolysaccharide. 1. TI-1 aitigen 2. TI-2 antigen

5. TI-1 antigen: also named B cell mitogen • Contains B cell mitogen and repeated B epitopes • Can induce immature and mature B cell-mediate immune response • In high concentrations, can induce polyclonal B-cell activation • In lower concentrations, only the BCR-binding TI-1 antigens can activate B cells • Not able to induce Ig class switch, antibody affinity maturation and memory B cells

6. TI-1 antigen in high concentrations B-cell mediate recognition and immune response to TI-1 antigens polyclonal B-cell activation non-specific antibody response TI-1 antigen in lower concentrations Specific antibody response to TI-1 antigen

7. TI-2 antigen • Only contains multitude repeated B-cell epitopes • Merely induces mature B cell-mediated immune response • Unresponses or hyporesponsive to infantile B cells • Activates the B-1 cells

8. TI-2 antigen alone activates B cells to secrete antibodies cell B cell-mediate recognition and immune response to TI-2 antigens Plasma cell

9. TI antigen mainly activates CD45+ B1 cells • The produced antibodies are mainly IgM • No MHC-restriction, without APC and Th cell help • Can not induce antibody class switch, affinity maturation and memory B cells

10. （二）B cell-mediate recognition to TD antigens • BCR binds to antigen specifically and transfer the antigen stimulatory signal into B cells • BCR specific binding to the antigen and intake it through internalization, then the antigen was degradated into peptides and the peptide-MHC-II molecule complex was formed, which can be recognized by antigen specific Th cells

11. Comparison of TD antigen with TI-1 and TI-2 antigens

12. 二. Activation of B Cells 1）The specific antigenic recognition signal of B cell activation (first signal)

13. B cell coreceptor complex The first signal of B cell activation

14. 2）Costimulatory signal of B cell activation (second signal) With the help of T cells 1.The activation of naïve Th cell

15. 2. The combination of Th cell and specific B cell TCR presented on Th cells specifically recognizes and binds antigenic peptide-MHC-II complex displayed on B cell surface The interaction of many adhesion molecular pairs makes the binding tighter.

16. ☆Direct contact T cells express CD40L，LFA-1，CD28, et al. CD40/CD40L，ICAM-1/LFA-1，B7/CD28 The most important molecule is CD40L(CD154)

17. B cell Th cell antigen Signal 1 Th activation Presentation of antigen Signal 2 Signal 2 Signal 1 B activation

18. 3. The activation of specific B cells Th cells can be induced to express many membranous molecules, for instance CD40L The dark zone formation of the germinal center in lymph follicles The clonal proliferation of B cells B cells are differentiated to the cells in the germinal center The formation of memory B cells

19. The function of cytokines IL-2, IFN- secreted by Th1 cells IL-4、IL-5、IL-6 secreted by Th2 cells

20. TD antigen B cell Th cell cytokines B cell

21. 三. The signal transduction of B cell activation （一）the antigen recognition structure of B cells

22. Signal transduction in B cells

23. 4. differentiation and maturation of B cells in the germinal center • FDC, B cell interaction ---B cell uptake antigens. • Antigen uptaken, process and presentation by B cells. • T, B cell interaction---Th cell activation. • CD40L upregulation and cytokine secretion in activated Th cells---further differentiation and maturation of B cells.

24. Centroblasts ↓ centrocytes Germinal center Blast proliferated B cells: mantle zone formation Non-proliferated B cells:

25. B cell activation and GC formation

26. (1) receptor editing Further immunoglobulin gene rearrangement in seconary lymph organs---some potentially self-reactive B cells may be rescued. Otherwise, self-reactive B cells undergo apoptosis or anergy.

27. (2) somatic hypermutation and affinity maturation Ig+ B cells proliferate rapidly, and their already rearranged receptor genes undergo further diversification. Some further diversifided Ig+ B cells acquir more affinitive BCR.

28. B cell maturation, migration and GC formation B cell proliferation somatic hypermaturation antigen recognition and affinity maturation no antigen loading B cells undergoing cell death generation of plasma or memory B cells B cell differentiation and maturation in germinal center

29. (3) immunoglobulin class switch

30. (4) destiny of maturated GC B cells • plasma cell, PC • memory B cell

31. (6) Humoral immune response • Primary immune response • Secondly immune response or • anamnestic response

32. Primary immune response ☆lag phase ☆log phase ☆steady-state phase ☆decline phase

33. Antigen Steady-state phase Lag phase Antibody titer Log phase Decline pahse Time

34. Secondly immune response or anamnestic response： • Short lag phase • longer steady-state phase • lower dose of antigen needed • mainly IgG • highly avidity

36. Master the general rule of B cell mediated immune response angainst TD-Ag. • Master similarities and differences betweenTI-Ag and TD-Ag inducing B cell immune response. • Understand mucosal immune response. • Understand mature , somatic hypermutation and affinity maturation and class switch of B cell.