医学免疫学英文版教学课件：Chapter 12 B Lymphocytes

《医学免疫学英文版教学课件：Chapter 12 B Lymphocytes》由会员分享，可在线阅读，更多相关《医学免疫学英文版教学课件：Chapter 12 B Lymphocytes（55页珍藏版）》请在装配图网上搜索。

1、Chapter 13 B LymphocytesLymphocytesContents B cell Maturation in the bone marrow B Cell Receptor and B Cell Accessory Molecules B cells subsetsDevelopment and differentiation of B cellsDevelopment of B cells in bone marrow-Ag independentDevelopment of B cells in peripheral lymphoid tissue-Ag depende

2、nt I.Differentiation of B cells in Bone marrow-Ag independent1.Bone marrow and its microenviroments：B cells need direct contact with stoma cells(including epithelial cells,fibroblasts and macrophages)Adhesion molecules and cytokines are involved in this process,eg.IL-7 which are produced by stoma ce

3、lls2.Process 2.Process:hemopoietic stem cells lymphoid progenitorpro-B cells(B220,heavy chain gene rearrangement,chain)pre-B cell(surrogate light chain+chain)immature B(chain or chain+chain mIgM,)negative selectionmature B(mIgM,mIgD)B repertoire 3.Events in the differentiation of B cells1)Negative s

4、election-self tolerance2)gene rearrangement-diversity of Ab1)Negative selection-self tolerance Immature B cells:mIgM-self antigen mIgM-self antigen apoptosis or anergy surviving to develop mature B cells Gene structure of Ig Gene rearrangement of Ig Allelic exclusion and Isotype exclusion Expression

5、 of Ig functional BCR/Ab expression(1)Germ-line gene structure of BCRThree gene familiesL chain:No.2 chromosome :No.22 chromosomeH chain:No.14 ChromosomeH chain:14 chromosomeV region encoding genes:VH(variable gene segments)48 DH(diversity gene segments)23 JH(joining gene segments)6 Leader sequences

6、ignal peptide C region encoding genes:CH(constant gene segments):C,C,C et al.(9)L chain(-2 chromosome,-22 chromosome)V region encoding genes:-V,J 40,5 -V,J 30,4 Leader sequencesignal peptide C region encoding genes:C(1);C(4)In heavy chains,the V,D and J segments encode the variable domain while the

7、C segment encodes the constant domain.In light chains,the V and J segments encode the variable domain whilethe C segment encodes the constant domain.33335032660513074C 1C 2C 4C C 2C C C C H chain:VDJ rearrangement of V gene and isotype switch of C gene V-J rearrangement of L chain (2)Gene rearrangem

8、ent of Ig VDJ rearrangement of H chain pro-B cells:D-J V-DJ VDJ DNA pre-B cells:VDJC VDJ-C RNA mRNA splicing V-J rearrangement of L chain pre-B cells:V-J VJ DNA immature B cells:VJC VJ-C RNA mRNA splicingMechanisms of Ig gene rearrangement recombination activating gene-and-2,RAG-1 and RAG-2 recognit

9、ion signal sequences，RSS Allelic exclusion and Isotype exclusion Allelic exclusion:Only one of the two alleles in homologous chromosomes can be expressed.Isotype exclusion:Only one of the two types of light chain genes can be expressed(:=65:35).(3)Characteristics of BCR gene rearrangement：Kuby Figur

10、e 5-10Allelic exclusionRead Kuby pages 115-117:Allelic Exclusion Ensures a Single Antigenic Specificity(4)The expression of BCR Intranuclear:DNA rearrangement -V region encoding gene(VDJ or VJ)Transcription and splicing -leader sequence+V region encoding gene+C region encoding gene (L gene-V gene C

11、gene)Extranuclear:Translation -nascent peptide L-V-CEndoplasmic reticulum:Assembly-H chain and L chain(IgM or IgD)Golgi complex:Transportation-BCR(membrane Ig,mIg)Pro-B cellCD45RPre-B cellheavy chainrearrangementexpresses IgM with surrogate light chainlight chain rearrangementImmature B cellB cell r

12、eceptortesting for binding to self proteinsMature B cellIgMIgDII.Development of B cells in peripheral lymphoid tissue-Ag dependantVirgin B/naive B more diePlasma cell AbMemory B 1.Important events in maturation outside the bone marrow-Ag dependantSomatic hypermutation Affinity maturationClass switch

13、ing(1)Somatic hypermutation Ag Activated B cell proliferate Gene mutation in V region encoding genes Affinity maturation(2)Class switching Ag Activated B cell proliferate VDJ is switched to recombine with another C region encoding gene Class switching IgM IgG,IgA,IgE2.Mechanism of Ig diversityV regi

14、on encoding genes of H chain:VH(variable gene segments)48 DH(diversity gene segments)23 JH(joining gene segments)6 V (40);J(5)V (30);J (4)human Ig:48VH23DH 6JH=6624 40V 5J =300 30V 7J =210(3)imprecise joining:random recombination or losing of several nucleotides in V-DJ,D-J or VJ junctionsN/P-nucleo

15、tides addition:Addition of several nucleotides in the region of VD and DJ junctions without template(N-nucleotide addition)or with template(P-nucleotide)There is no N-nucleotides addition in L chain(4)Combination of heavy and light chain(5)Receptor editing:immature B cells which recognize self antig

16、ens reactivate the RAG leading to rearrangment of/genes(new BCR)Part III Surface membrane molecule on B cells and their functionsAntigen receptor complex:recognizing antigenAccessory membrane molecules related to the activation of B cellsOther surface membrane moleculesI.Antigen receptor complex-BCR

17、 and BCR complex1.BCRMembrane immunologlobulin(mIg)on B cell:mIgM,mIgD -Bind antigen specifically2.BCR complex:BCR and 2 Ig-(heterodimer)Ig-(CD79a),Ig-(CD79b)ITAM-bind to tyrosine kinase -transduct an activated signalII.Accessory membrane molecules on B cells1.co-receptor complex:CD19,CD21,CD81 CD19

18、:Transduct activatory signal into B cell CD21(CR2):receptor of C3dg,C3d and iC3b -Enhance the binding of BCR and antigen -pass activation signal to CD19 -EB virus receptorRole of complement in B cell activation2.CD40-co-stimulatory receptor CD40 on B cell binds to CD40L on activated T cell -Transduc

19、t an important costimulatory signal to B cells 3.Co-stimulatory molecules:CD80(B7-1)and CD86(B7-2)4.ICAM-1 and LFA-1ICAM-1LFA-1LFA-1ICAM-1B7CD28CD40CD40LTCRMHC-IICD4CD3III.Other surface membrane molecules1.Mitogen receptor:SPA,LPS-Activate B cell only2.Class I and class II MHC molecules3.Cytokine re

20、ceptor:IL-1R,IL-2R Part IV Subgroups of B cellAccording to expression of CD5 or notB1 cell(CD5+)B2 cell(CD5-)Comparison of B1 and B2 cells B1 B2 Development early late BCR mIgM mIgM and mIgD CD5 +-Reproduction self-renewing from pre-B cell in BM Recognized Ag TI-Ag and auto-Ag TD-Ag Ab type mainly I

21、gM mainly IgG Ab avidity low high Second IR -+Function innate immunity adaptive immunity What you should know by the end of this lectureDefinition of TCR and TCR complex,ITAM and ITIM,BCR and BCR complexMajor surface membrane molecules on T/B cell and their functionsMain characteristics of subgroups of T/B cells