White pulp reconstitution after human bone marrow transplantation.

To reveal the reconstitution process of the white pulp after bone marrow transplantation (BMT), spleens of 24 marrow recipients whose survival times ranged from 34 to 303 days after BMT, were analyzed at the histopathological and immunohistochemical level. Up to 3 months after BMT, the white pulp was atrophic and consisted mainly of T cells forming periarteriolar lymphatic sheaths (PALS). Approximately 100 days after BMT, B cells aggregated in some of the white pulp, forming primary follicles, whereas marginal zones could not be detected. Beyond 4 months after BMT, the PALS, the lymphoid follicle, and the marginal zone of the white pulp could be seen in most of the recipients' spleens. However, the recovery of the marginal zone was poor up to 10 months after BMT. Thus, the white pulp was reconstituted sequentially, beginning in the PALS, followed by reconstitution in lymphoid follicles, and finally in the marginal zone. The development of the PALS corresponded well with the appearance of interdigitating dendritic cell, as did the development of lymphoid follicles with the appearance of follicular dendritic cell. The sequential reconstitution of the white pulp demonstrated in this study provides the morphological basis for the functional immune recovery of marrow recipients. In particular, the delay of the marginal zone reconstitution seems to be responsible for the functional asplenia of long-term survivors.