Initiation of antibody responses by different classes of lymphocytes. V. Fundamental changes in the physiological characteristics of virgin thymus-independent ("B") lymphocytes and "B" memory cells.

The life-span and migratory characteristics of rat thoracic duct cells which initiate the adoptive primary and secondary antibody response to diphtheria toxoid (DT) and horse spleen ferritin (HSF) were investigated. The experimental results show that thoracic duct lymphocytes from normal (unimmunized) donors are able to restore the adoptive response of irradiated hosts to HSF. Thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) showed a marked reduction in their restorative action as compared with unpassaged cells. In addition, the restorative action of cells from donors treated with thymidine-(3)H for 48 hr before cannulation of the thoracic duct was markedly decreased. This indicates that a population of lymphocytes involved in the adoptive primary response is unable to recirculate from the blood to the lymph and is turning over rapidly (short lived). The nonrecirculating, short-lived lymphocytes are proably "B" cells, since a combination of spleen cells from neonatally thymectomized rats and passaged or thymidine-(3)H-treated cells restores a vigorous response to HSF. On the other hand, passaged or thymidine-(3)H-treated thoracic duct cells from donors immunized to DT or HSF are able to restore a vigorous adoptive secondary antibody response. Experiments with the hapten-protein conjugate, DNP-DT, show that the majority of both helper ("T") and precursor ("B") cells are able to recirculate and are slowly turning over (long lived). The findings suggest that T lymphocytes involved in both the primary and secondary antibody response are recirculating, long-lived cells. However, B lymphocytes involved in the primary response are nonrecirculating, short-lived cells ("B(1)" cells) which undergo a fundamental physiological change to recirculating, long-lived cells ("B(2)" cells) involved in the secondary antibody response.