Sympathetic innervation of the amphibian spleen: Developmental studies in Xenopus laevis

Larval Thymectomy of Xenopus laevis

“…Additionally, the frog undergoes class switch recombination of the immunoglobulin heavy chain locus in a translocon organization and somatic hypermutation driven by specialized follicular antigen presentation (Neely et al 2018). The frog thymectomy model has been used for decades (Horton and Manning 1972) and is now an established model of adaptive immunity absent the effect of T cells in a metamorphosing tetrapod vertebrate (see, e.g., Sakuraoka and Tochinai 1993;Ono and Tochinai 1995;Kinney et al 1996;Robert et al 1997;Horton et al 2003;Mashoof et al 2013). The relatively superficial position of the bilateral organ in developing anuran amphibians makes the frog thymectomy model straightforward.…”

Neural-immune system interactions in Xenopus

“…Interactions between development of innervation and immune system reorganization appear to be complex and dynamic as might be expected in such a rapidly changing system. Splenic innervation is observable as early as Nieuwkoop and Faber (61) larval stage 54 (62), with a drop in splenic NE levels (assessed by HPLC and SPG histofluorescence, (63)) at stage 58, a developmental point at which lymphocyte numbers and their mitogen responsiveness have also been reported to decrease (64). The adult pattern of innervation confined to white pulp then emerges at metamorphic climax (65).…”

“…However, early larval thymectomy which renders animals T-deficient does not alter the development of normal innervation (66,67). Prevention of overt metamorphosis by sodium perchlorate blockade (68) prevented the development of NA splenic innervation in some, but not all, tadpoles examined (62). Further, chemical removal of sympathetic innervation during larval life prior to the appearance of splenic compartmentation did not alter the subsequent appearance of distinct red and white pulp compartments (62).…”

“…It is thought that such allotolerance is a reflection of the tolerance that must develop to new self-antigens that emerge during this transition from immunocompetent larva to immunocompetent adult. Chemical SyX also had no discernible effect on the development of tolerance of perimetamorphic animals to skin allografts from adult donors differing at only minor H loci (84). Given that tolerance induction during metamorphosis is critical for a successful transition, it is perhaps not surprising that there is no effect of the sympathetic nervous system on the process.…”

“…Other morphologic and functional features of immunity do not change in perchlorate-blocked tadpoles, and thus are (directly or indirectly) thyroid dependent. For example, in blocked larvae: the thymus does not assume an adult-type morphology (112); splenic compartmentation and innervation by the SNS (described above) is dramatically delayed (62); and lymphocytes in the thymus and spleen do not achieve the expanded cell numbers characteristic of postmetamorphic adults (113,114). Functionally, blocked larvae retain: larval-type tolerogenic responses to skin allografts (Cohen and Crosby, unpublished), larval patterns of antibody response to a specific hapten (111); and a lack of adulttype MHC Class II + T cells in the periphery (113).…”