B-cell development in the amphibian Xenopus

The amphibian Xenopus and mammals have similar organization and usage of th eir immunoglobulin gene loci with combinatorial joining of V, D and J eleme nts. The differences in B-cell development between mammals and this amphibi an are due to major differences in developmental kinetics, cell number and lymphoid organ architecture. Unlike mammals, the immune system of Xenopus d evelops early under pressure to develop quickly and to produce a heterogene ous repertoire before lymphocyte numbers reach 5,000, thereby imposing a li mitation on clonal amplification. In addition, it is submitted to metamorph osis. Thus, during the early antigen-independent period, several features o f B-cell development related to immune diversification are under strict gen etically preprogramed control: 1) D reading frames contribute complementary determining region 3 with features that occur in mammals by somatic select ion, 2) the temporal stepwise utilization of V-H genes in Xenopus occur in families probably because of structural DNA features rather than their posi tion in the locus. Larval and adult immune responses differ in heterogeneit y. Larval rearrangements lack N diversity. During the course of immune resp onses, somatic mutants are generated at the same rate as in other vertebrat es but are not optimally selected, probably due to the simpler organization of the lymphoid organs, with neither lymph nodes nor germinal centers resu lting in poor affinity maturation. Switch from IgM to other isotypes is med iated by loop-excision deletion of the IgM constant region gene via switch regions which, unlike their mammalian counterpart, are A-T rich and reveal conserved microsites for the breakpoints.