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B lymphocyte-mediate recognition of antigens and the immune response 1. B cell-mediate immune response to T-dependent antigen 2. B cell-mediate immune response to T-independent antigen 3. The general rule of humoral immune response Humoral immunity: A immune response mediated by B lymphocyte-secreted antibodies. Its funtion is to neutralize and eliminate the antigens which induced the antibodies. 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 TI-1 antigen: also named B cell mitogen 1. Contains B cell mitogen and repeated B epitopes 2. Can induce immature and mature B cell-mediate immune response 3. In high concentrations, can induce polyclonal B-cell activation 4. In lower concentrations, only the BCR-binding TI-1 antigens can activate B cells 5. Not able to induce Ig class switch, antibody affinity maturation and memory B cells TI-1 antigen in high concentrations polyclonal B-cell activation non-specific antibody response TI-1 antigen in lower concentrations Specific antibody response to TI-1 antigen B-cell mediate recognition and immune response to TI-1 antigens TI-2 antigen A. Only contains multitude repeated B-cell epitopes B. Merely induces mature B cell-mediated immune response C. Unresponses or hyporesponsive to infantile B cells D. Activates the B-1 cells TI-2 antigen alone activates B cells to secrete antibodies cell B cell-mediate recognition and immune response to TI-2 antigens Plasma cell • 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 （二）B cell-mediate recognition to TD antigens 1. BCR binds to antigen specifically and transfer the antigen stimulatory signal into B cells 2. 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 Comparison of TD antigen with TI-1 and TI-2 antigens TD antigen TI-1antigen TI-2 antigen Infantile Ab response ＋ ＋ － Ab response in nude mice － ＋ ＋ Ab response without T cells － ＋ － Activated T cells ＋ － － Polyclonal activated B cells － ＋ － Need the repeated sequence or not － － ＋ Bacterial antigen diphtheria toxin lipopolysaccharide capsular polysaccharide 二. Activation of B Cells 1）The specific antigenic recognition signal of B cell activation (first signal) B cell coreceptor complex The first signal of B cell activation 2）Costimulatory signal of B cell activation (second signal) With the help of T cells 1.The activation of naïve Th cell 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. ☆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) B cell antigen Th cell Signal 1 Th activation Presentation of antigen Signal 2 Signal 1 Signal 2 B activation 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 The function of cytokines IL-2, IFN- secreted by Th1 cells IL-4、IL-5、IL-6 secreted by Th2 cells TD antigen B cell Th cell B cell cytokines 三. The signal transduction of B cell activation （一）the antigen recognition structure of B cells Signal transduction in B cells 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. Germinal center Blast proliferated B cells: Non-proliferated B cells: Centroblasts ↓ centrocytes mantle zone formation B cell activation and GC formation (1) receptor editing Further immunoglobulin gene rearrangement in seconary lymph organs---some potentially selfreactive B cells may be rescued. Otherwise, self-reactive B cells undergo apoptosis or anergy. (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. 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 (3) immunoglobulin class switch (4) destiny of maturated GC B cells 1. plasma cell, PC 2. memory B cell (6) Humoral immune response • Primary immune response • Secondly immune response or anamnestic response Primary immune response ☆lag phase ☆log phase ☆steady-state phase ☆decline phase Antigen Antibody titer Lag phase Log phase Steadystate phase Decline pahse Time Secondly immune response or anamnestic response ： 1. Short lag phase 2. longer steady-state phase 3. lower dose of antigen needed 4. mainly IgG 5. highly avidity Master the general rule of B cell mediated immune response angainst TD-Ag. Master similarities and differences between TI-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.