title: What limits affinity maturation of antibodies in Xenopus--the rate of somatic mutation or the ability to select mutants?
abstract: Although the Xenopus immunoglobulin heavy chain locus is structurally and functionally similar to mammalian IgH loci, Xenopus antibodies are limited in heterogeneity, and they mature only slightly in affinity during immune responses. During the antibody response of isogenic frogs to DNP-KLH, mu and upsilon cDNA sequences using elements of the VH1 family were cloned, sequenced and compared with germline counterparts. There were zero to four mutations per sequence, mostly single base substitutions, in the framework and CDRs 1 and 2 of VH. No mutations were found in JH. Since the point mutation rate was only 4- to 7-fold lower than that calculated for mice, affinity maturation does not seem to be limited by mutant availability. Because of a relatively low ratio of replacement to silent mutations in the CDRs and a very high ratio of GC to AT base pairs altered by mutation, it is suggested that the problem results from the absence of an effective mechanism for selecting mutants, which in turn might be related to the absence of germinal centers in Xenopus.
authors.affiliation: Basel Institute for Immunology, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Wilson
authors.forename: E
authors.initials: E
authors.lastname: Hsu
authors.forename: A
authors.initials: A
authors.lastname: Marcuz
authors.forename: M
authors.initials: M
authors.lastname: Courtet
authors.forename: L
authors.initials: L
authors.lastname: Du Pasquier
authors.forename: C
authors.initials: C
authors.lastname: Steinberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000235:genetics*; D001483:Base Sequence; D004247:DNA; D004252:DNA Mutational Analysis; D006433:Hemocyanins / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D014982:Xenopus laevis
chemical_list: D007143:Immunoglobulin Heavy Chains; D004247:DNA; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin