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1、Chapter 11 Cells of adaptive immune response :B lymphocytesINTRODUCTIONn norigin:bone marrown nbasic function: humoral immune responseChapter 11 Cells of adaptivSection 1 membranous molecules on B lymphocyte and functions 一、一、B cell receptor ，BCR Constitution of BCR complex：mIg（IgM and IgD）and Ig （C
2、D79a）/Ig （CD79b）Section 1 membranous molecules基础医学院医学免疫学-chapter11课件1 1、mIgmIgStructureStructure：mIg consist of a basic unit of mIg consist of a basic unit of four polypeptide chains,two identical H four polypeptide chains,two identical H chains and two identical L chains.chains and two identical L
3、chains.Intracellular region is very short. immature Intracellular region is very short. immature B cells express mIgMB cells express mIgM， mature B cells mature B cells express mIgM and mIgD simultaneouslyexpress mIgM and mIgD simultaneously，plasma cells dont express Ig. plasma cells dont express Ig
4、. FunctionFunction：specific binding antigen specific binding antigen 1、mIg2 2、IgIg /Ig/Ig Structure Structure ： Ig Ig （CD79aCD79a）and Igand Ig （CD79bCD79b）belong to Ig gene surperfamilybelong to Ig gene surperfamily，consist of extracellular regionconsist of extracellular region，transmembrane region
5、and cytoplasma transmembrane region and cytoplasma regionregion，IgIg and and IgIg held together by held together by disulfide bond to form disulfide bond to form heterogenous heterogenous dimer,then form BCR-Igdimer,then form BCR-Ig /Ig/Ig complex complex with BCR.with BCR. FunctionFunction：1 1、 tra
6、nsducing antigen-binding signal to B transducing antigen-binding signal to B cellcell2 2、 transferring Ig from inner of cell to outer transferring Ig from inner of cell to outer of cellof cell2、Ig/Ig Distribution of BCR complex：n nmature B cell and immature B celln npre-B receptor consists of chain、
7、substitute L chain and Ig /Ig ， pre-B receptor expressing on the surface of pro-B cell，is really important for B cell development in bone marrow.Distribution of BCR complex：基础医学院医学免疫学-chapter11课件1213141516171819203456789111210Lymphocytes have unique, clonally distributed antigen receptors10101010101
8、0101010101010101010101010AntibodiesB cells121314151617181920345678911121二、二、co-receptor1、CD19/CD21/CD81/CD225StructureStructure and DistributionDistribution ：The co-receptor on the surface of B cell is composed of CD19、CD21 and CD81/CD225（Leu-13）with non-covalent bond.ligand：C3dg , C3d, iC3bfunction
9、：enhance the sensitivity of B cell to antigen stimulus二、co-receptor1、CD19/CD21/CD81/基础医学院医学免疫学-chapter11课件2 2、CD72CD72n nStructureStructure: Belongs to C-type lectin : Belongs to C-type lectin superfamily, is a 45kDa II-type superfamily, is a 45kDa II-type transmembranous proteintransmembranous prot
10、ein. . n nDistributionDistribution:Constituent expression on :Constituent expression on every stage B cells except plasma cells. every stage B cells except plasma cells. Contain 2 ITIMContain 2 ITIMn nLigandLigand：CD100,expressed on most CD100,expressed on most hemocytoblast including B and T cells.
11、 hemocytoblast including B and T cells. CD100 interacting with CD72 can CD100 interacting with CD72 can eliminate the inhibition by CD72eliminate the inhibition by CD72，enhancing the effect of signal 1 . enhancing the effect of signal 1 . n nFunctionFunction:When BCRs cross link, it can :When BCRs c
12、ross link, it can inhibit the stimulation of signal 1.inhibit the stimulation of signal 1.2、CD72三、三、 co-stimulation molecules1 1、CD40CD40StructureStructure: Belonging to: Belonging to TNFRSFTNFRSFDistributionDistribution： Constituent expression on Constituent expression on mature B cellmature B cell
13、LigandLigand：CD40L/CD154CD40L/CD154（ expression on expression on activated T cellsactivated T cells）FunctionFunction：play an very important role in B play an very important role in B cell differentiation and maturecell differentiation and mature三、 co-stimulation molecules1、C2 2、CD80/86CD80/86Structu
14、reStructure: another name : another name B7.1B7.1（CD80CD80）/B7.2/B7.2（CD86CD86），），），）， is single is single chain chain transmembrane glycoproteintransmembrane glycoproteinDistributionDistribution：expression on expression on actived B actived B cellscellsLigandLigand：CD28CD28、 CTLA-1 CTLA-1（ expressi
15、on on expression on activated T cells activated T cells ）FunctionFunction：offer co-stimulating signal for T offer co-stimulating signal for T cell activationcell activation（because B cell is APC because B cell is APC ）2、CD80/86基础医学院医学免疫学-chapter11课件3、CD27Structure： Belonging to TNFRSF。Distribution：
16、CD27（ activated B cells ）Ligand：CD70（ CD154+CD70+T cell）Function： Play a role in B cell differentiating to plasma cellsBTCD27CD70CD70CD273、CD27BTCD27CD704 4、CD70CD70ExpressionExpression： activated B cells activated B cellsLigand Ligand ： CD27 CD27 （CD45RACD45RA+ +CD4CD4+ + T cell T cell）FunctionFunc
17、tion： Play a role in CD45RA Play a role in CD45RA+ +CD4CD4+ + T T cells differentiating to regulatory T cells cells differentiating to regulatory T cells to inhibit the production of Ab. to inhibit the production of Ab. 5 5、othersICAM-1ICAM-1、LFA-1 etc.LFA-1 etc.4、CD70四、四、 membrane-binding molecules
18、 of mitogen LPS receptor、PWM receptor五五、other membrane molecules1、CD20：Distribution：expressed on every stage B cells except for plasma cells.Function：Regulate the proliferation and differentiation of B cells .四、 membrane-binding molecules 2 2、CD22CD22：DistributionDistribution： Expresses on B cells E
19、xpresses on B cells speciallyspecially， and doesnt express on and doesnt express on plasma cellplasma cellLigand Ligand ：CD45ROCD45RO、CD75 CD75 （唾液酸聚糖分子）（唾液酸聚糖分子）（唾液酸聚糖分子）（唾液酸聚糖分子）FunctionFunction：Binding CD45ROBinding CD45RO、CD75CD75，mediate interaction on B-monocytemediate interaction on B-monocyt
20、e、B-TB-T、B-B .B-B .3 3、CD32CD32：Fc Fc R II-BR II-B2、CD22：基础医学院医学免疫学-chapter11课件Section 2 Subgroup of B cellsB-1 cellB-1 cell：CD5+ CD5+ ，appears on individual appears on individual development forepart development forepart ，locate in peritoneumlocate in peritoneum、pleura etc. pleura etc. innate immun
21、ityinnate immunity，play a role in mucous play a role in mucous membrane immunitymembrane immunityAntigen of stimulating Antigen of stimulating ： LPS LPS（ lipid polysaccharides lipid polysaccharides ）Production antibodyProduction antibody：IgMIgM Polyreactivity Polyreactivity ： B-1 cell antigen recept
22、or and B-1 cell antigen receptor and antibody can bond all kinds of antigen epitope using antibody can bond all kinds of antigen epitope using relatively low affinityrelatively low affinitySection 2 Subgroup of B cellsFunctions of B-1 cells：1、anti-microbe infection by producing anti bacteria antibod
23、y. 2、clearing degenerative self-antigen by producing poly-reactive autoantibody3、inducing autoimmune disease by producing pathogenic autoantibody.Functions of B-1 cells：B-2 cellB-2 cell： ordinary ordinary B cellB cell，CD5-CD5-，Contain tow subsets of MZContain tow subsets of MZ（marginal marginal zone
24、zone）and follicular and follicular MZ B cell is the first line of defenceMZ B cell is the first line of defenceFO B cell participates later antibody FO B cell participates later antibody response of T cell dependentresponse of T cell dependentThe most B cell in Peyers patches The most B cell in Peye
25、rs patches （PPPP）in GALT is B-2 cellin GALT is B-2 celladaptive immunityadaptive immunityB-2 cell： ordinary B cell，CD5-Similarities and differences of B-1 cell and Similarities and differences of B-1 cell and B-2 cellB-2 cell性质性质性质性质B-1B-1细胞细胞细胞细胞B-2B-2细胞细胞细胞细胞CD5CD5+ +- -初次产生的时间初次产生的时间初次产生的时间初次产生的时
26、间胎儿期胎儿期胎儿期胎儿期出生后出生后出生后出生后存在部位存在部位存在部位存在部位腹膜腔、胸膜腔、肠道固有层腹膜腔、胸膜腔、肠道固有层腹膜腔、胸膜腔、肠道固有层腹膜腔、胸膜腔、肠道固有层广泛广泛广泛广泛更新方式更新方式更新方式更新方式自我更新自我更新自我更新自我更新由骨髓产生由骨髓产生由骨髓产生由骨髓产生自发性自发性自发性自发性IgIg的产生的产生的产生的产生高高高高低低低低特异性特异性特异性特异性多反应性多反应性多反应性多反应性单特异性，尤在免疫后单特异性，尤在免疫后单特异性，尤在免疫后单特异性，尤在免疫后分泌的分泌的分泌的分泌的IgIg的同种型的同种型的同种型的同种型IgMIgGIgMIg
27、GIgGIgMIgGIgM体细胞高频突变体细胞高频突变体细胞高频突变体细胞高频突变低低低低/ /无无无无高高高高对碳水化合物抗原的应对碳水化合物抗原的应对碳水化合物抗原的应对碳水化合物抗原的应答答答答是是是是可能可能可能可能对蛋白质抗原的应答对蛋白质抗原的应答对蛋白质抗原的应答对蛋白质抗原的应答可能可能可能可能是是是是功能功能功能功能参与固有免疫参与固有免疫参与固有免疫参与固有免疫参与适应性免疫参与适应性免疫参与适应性免疫参与适应性免疫Similarities and differences ocharactercharacterB-1 B-1 B-2B-2CD5CD5+ +- -First
28、timeFirst timebeginbegin初次产生的时间初次产生的时间初次产生的时间初次产生的时间Fetus timeFetus timeAfter birthAfter birthLocationLocationPeritoneum/pleuraPeritoneum/pleura、intestines intestines 固有层固有层固有层固有层EverywhereEverywhereRenewalRenewalSelf renewalSelf renewalBone marrowBone marrowSpontaneous Ig productionSpontaneous Ig p
29、roductionHighHighLowLowspecificityspecificityPolyreactivityPolyreactivitySingle specificity, Single specificity, especially after especially after immunityimmunityIsotypesIsotypesIgMIgGIgMIgGIgGIgMIgGIgMSomatic hypermutation of IgSomatic hypermutation of IgNoNo/low/lowhighhighImmunity to Immunity to
30、 Immunity to Immunity to CarbohydrateCarbohydrateyesyesmaymayImmunity to ProteinImmunity to ProteinmaymayyesyesfunctionfunctionInnate immunityInnate immunityAdaptive immunityAdaptive immunitycharacterB-1 B-2CD5+-First timSection 3 function of B cell（一）（一）produce antibodies1、 neutralization: bacteria
31、 toxin ,pathogen2、 opsonization：Ab、complement3、antibody-dependent cell-mediated cytotoxicity（ADCC）4、 activate Complement : opsonization and lyse microbeSection 3 function of B cell基础医学院医学免疫学-chapter11课件基础医学院医学免疫学-chapter11课件基础医学院医学免疫学-chapter11课件（二）（二）antigen presenting ： activated B cells presentin
32、g soluble Ag（二）antigen presenting ：（三）（三）immunoregulation ：positive and negative regulationn nActivate MActivate M & FDC & FDC ：IFN-IFN- 、TNFTNF、IL-6IL-6、GM-CSFGM-CSFn ninhibit Minhibit M & FDC & FDC ：IL-4IL-4、IL-10IL-10、TGF-TGF- ；n nActivate NK: IL-12Activate NK: IL-12、IFN-IFN- 、IFN-IFN- 、 IL-2 IL-2 ， inhibit NK: TGF- inhibit NK: TGF- ；n nInduce inflammatory cells refresh by Induce inflammatory cells refresh by chemotaxischemotaxis：IL-8IL-8、G-CSFG-CSF、GM-CSFGM-CSF；n nCo-stimulate T proliferationCo-stimulate T proliferation：IL-1 IL-1 、IL-IL-1 1 、 TNF TNF、GM-CSFGM-CSF（三）immunoregulation ：
