醫(yī)學(xué)免疫學(xué)課件：B Lymphocytes

1、B LymphocytesB LymphocytesImmunity： Innate immunity：Macrophages Dendritic cells Neurophils etc. Adaptive immunity: T lymphocytes B lymphocytesLymphocytesContents: B LymphocytesB Cell Development B Cell Surface Molecules B Cell SubsetsContents: B LymphocytesB Cell Development B Cell Surface Molecules

2、 B Cell SubsetsClone deletion Receptor editingB Cell DevelopmentB Cell DevelopmentB Cell DevelopmentBCR genes (Ig genes): L chain: VL, CL H chain: VH, CHB Cell DevelopmentB Cell DevelopmentRandom Recombination Heavy Chain Recombination Light Chain RecombinationB Cell Development Allelic exclusion Li

3、ght chain isotype exclusionB Cell Development Allelic exclusion ：If a protein is produced from the recombined heavy chain locus on one chromosome, this receptor signals inhibit rearrangement of the heavy chain locus on the other chromosome. If the first rearrangement is nonproductive, the heavy chai

4、n allele on the other chromosome can complete VDJ rearrangement. If both alleles are non-functional in a developing B cell, that cell fails to receive survival signals and dies. Light chain isotype exclusion ：A protein production prevents rearrangement. If the rearrangement is nonproductive or a sel

5、f-reactive rearranged chain is deleted, rearrangement will occurs. As a result, an individual B cell clone can express only one of the two types of light chains. If both alleles of and chains are nonfunctional in a developing B cell, that cell fails to receive survival signals that are normally gene

6、rated by the BCR and dies. Allelic exclusion Light chain isotype exclusionEnsuring that every B cell will express a single receptor, produce a specific Ab.B Cell Development Gene recombination Recombinatorial inaccuracies N-nucleotide addition Receptor editing Somatic hypermutation (peripheral lymph

7、oid organs) Generation of BCR DiversityB Cell DevelopmentReceptor editingClonal deletion Receptor editing:In central immune organ, some immature B cells which recognize autoantigens may re-activate their RAG gene, induce rearrangement of V, J genes, synthesis a new light chain, result to change thei

8、r specificity of BCR.B Cell DevelopmentNegative Selection (receptor editing, clonal deletion):induce central tolerance, ensure BCR do not display self-reactivityPositive Selection：affinity maturation, enhance the ability of immune responseBB Cell DevelopmentSomatic hypermutation: High-frequency poin

9、t mutations in Ig VH and VL that occur in germinal center B cells. Mutations result in increased affinity of antibodies for antigen. Mutations impart a selective survival advantage to the B cells producing those antibodies and lead to affinity maturation of a humoral immune response.B Cell Developme

10、ntAg B Cells in Peripheral Lymphoid OrgansB Cell DevelopmentReceptor editingClonal deletion Contents: B LymphocytesB Cell Development B Cell Surface Molecules B Cell Subsets mIg: mIgM, mIgD Ig /Ig (CD79a/CD79b) BCR complex:B Cell Surface MoleculesCo-receptor:B Cell Surface MoleculesCD40: CD40-CD40LC

11、D80/CD86 (B7-1/2)： bind to CD28: activate T cells bind to CTLA-4: inhibit T cell activationCo-stimulatory Molecules:B Cell Surface Molecules ICAM-1（CD54） LFA-1（CD11a/CD18）Adhension Molecules:B Cell Surface MoleculesCytokine ReceptorsB Cell Surface MoleculesContents: B LymphocyteB Cell Differentiatio

12、n B Cell Surface Markers B Cell SubsetsB Cell SubsetsExpress the CD5 molecule Derive from fetal liver HSCA self-renewing populationDistinct from conventional Bs (B2 cells)First to appear in ontogenyExpress surface IgM, little or no IgDProduce IgM from minimally mutated germlineAbs are low affinity and polyreactiveB1:Abbas et al. Cellular and Molecular Immunology. 7eB2:Contents: B LymphocytesB Cell Development B Cell Surface Molecules B Cell SubsetsReview questions:1. Describe B cell subsets, function.2. Explain negative selection