Immunoglobulin Genes and B Cell Development in Amphibians

Abstract

Although all vertebrates can make antibodies, the different classes do not respond to antigenic challenges in exactly the same manner. The differences that one can observe from cyclostomes to mammals can be due to “inside” causes: structure of the Ig molecule, architecture of the Ig loci, properties of the lymphoid cells; or to “outside” causes: difference in selective pressures brought in, for instance, by general physiological differences such as cell cycle properties, developmental differences, etc. Among vertebrates, amphibians (Figure 1) certainly represent a class where the selection pressures are different from those encountered in mammals. Given their mode of development, the individual is exposed to antigen (in most cases) very early (2-4 days after fertilization) which may imply the development of a pressure to develop an immune system early when the total number of lymphocytes is small (orders of magnitude lower than in mammals). Tadpoles indeed produce antibodies but their repertoire is different from that of adults.¹ It is interesting to see how these conditions, unfamiliar to mammals, have influenced the immune system of the frog. From the study of antibody production in anurans and to a certain extent in urodeles, two observations emerged: a restricted heterogeneity of amphibian responses to various antigens (measured by counting isoelectro focusing spectrotypes of the low molecular weight antibodies IgY, see Figure 2) and the poor affinity maturation of the antibodies during the response (10 x at best, versus 10³ or 10⁴ fold in mammals).^1,2,3 Limited protein sequence data of H and L chains were consistent with a low heterogeneity of anti-DNP antibodies.⁴ Moreover, studies in genetically identical animals indicated a massive sharing of IEF spectrotypes and idiotypes between cloned individuals and their inheritance from one generation to the other.