抗体多样性是如何产生的.pptVIP

* How is antibody diversity generated? Two early theories: Germline hypothesis The genome contains many loci encoding antibody molecules. B cells express one of these loci. Different B cells express different loci. Somatic mutation hypothesis There are a small number of antibody genes which undergo mutation as the B cell matures - thus giving rise to B cells expressing antibody of different specificity. Three genetic loci encode immunoglobulin molecules: - two loci encoding the light chains - kappa locus - lambda locus - one locus encoding the heavy chain These three loci are located on different chromosomes. The loci encoding immunoglobulins have a unique structure. - composed of gene segments The heavy chain locus has multiple V (variable) segments, multiple D (diversity) segments, multiple J (joining) segments and multiple C (constant) segments. During maturation, one of each V, D and J segment is randomly “chosen” and used to encode the final antibody molecule. Germline configuration of the heavy chain locus (mice) Each gene segment may have its own intron-exon structure - e.g. the Cm gene segment… Kuby Figure 5-3 The kappa locus has a similar structure - BUT - does not have D segments. A kappa chain is encoded by one V segment, one J segment and one C segment. Kuby Figure 5-3 The lambda locus also has only V, J and C segments. Kuby Figure 5-3 Read Kuby pages 109-110: Multigene Organization of Ig Genes Kuby Figure 5-3 In heavy chains, the V, D and J segments encode the variable domain while the C segment encodes the constant domain. In light chains, the V and J segments encode the variable domain while the C segment encodes the constant domain. During B cell maturation, immunoglobulin genes undergo rearrangement. During B cell maturation, immunoglobulin genes undergo rearrangement. During B cell maturation, immunoglobulin genes undergo rearrangement. During B cell maturation, immunoglobulin genes undergo rearrangement. The kappa and lam