Mutation, selection, and memory in B lymphocytes of exothermic vertebrates

Unlike mammals, cold-blooded vertebrates produce antibodies of low heterogeneity that show little increase in binding affinity with time after immunization. In secondary responses, antibody titers and affinities are often little, if any, higher than in primary responses. That is, specificity, diversity, and memory--the hallmarks of the immune system--are rather meager in the humoral immune responses of exothermic vertebrates. As the genetic components of the immunoglobulin (Ig) gene systems in fishes, amphibians or reptiles are not deficient in number or diversity, their responses probably do not stem from restrictions in the primary antibody repertoire. Somatic hypermutation at the Ig locus, which generates diversity and higher affinity antibodies in mammals, is not lacking in the South African frog Xenopus or in the shark. However, the Ig mutants recovered are strongly biased toward alterations at GC pairs, an indication that they have not undergone effective selection. While cells resembling follicular dendritic cells are present in cold-blooded vertebrates, germinal centers do not form. It is suggested that this absence of germinal centers, the site of selection for the mutants with higher affinity receptors and of differentiation into memory B cells in mammals, may explain the principal differences between cold and warm-blooded vertebrates.