RELATIONSHIP OF GERMINAL CENTERS IN LYMPHOID TISSUE TO IMMUNOLOGICAL MEMORY : I. EVIDENCE FOR THE FORMATION OF SMALL LYMPHOCYTES UPON TRANSFER OF PRIMED SPLENIC WHITE PULP TO SYNGENEIC MICE

The fate, proliferation, and developmental potentialities of cell suspensions made from white pulp containing large germinal centers have been studied in the mouse by transfer of cells labeled with thymidine-3H to lethally irradiated, syngeneic recipients. Radioautographic analyses were made using both smears and sections of a variety of tissues. Thymidine-3H-labeling patterns of white pulp showed that, initially, labeling occurred in a majority of blast and "intermediate cells" but in very few or no small lymphocytes. After intravenous transfer, most of the labeled cells localized in the lymphoid tissues of spleen, lymph nodes, and Peyer's patches. Few cells migrated to the thymus, lung, liver, and intestinal mucosa. Both after intravenous and after intraperitoneal transfer there was a rapid increase in the incidence of labeled small lymphocytes and a decrease of labeled blasts and intermediate cells. This was accompanied by an increase in the grain count of the small lymphocytes and a progressive decrease in the grain counts of the blast cells. Exposure of nonlabeled donor cells to thymidine-3H at various time intervals after transfer indicated that dividing cells were present early after transfer but that their incidence progressively decreased. Between 24 and 48 hr, very little cell division was detectable

THE PROLIFERATIVE AND ANAMNESTIC ANTIBODY RESPONSE OF RABBIT LYMPHOID CELLS IN VITRO : II. REQUIREMENT FOR ADHERENT AND NONADHERENT CELLS OF THE RESPONSES TO PARTICULATE ANTIGENS IN SPLEEN CELL CULTURES

Both primary and secondary responses to sheep erythrocytes and to Brucella abortus antigen have been obtained in cultures of dispersed rabbit spleen cells. Removal of adherent cells by repeated incubation of spleen cells on absorbent cotton diminished the ability of the spleen cell suspensions to give secondary as well as primary responses in vitro. When comparing cultures made in dishes and in tubes, the loss of responsiveness after incubation on cotton was much more evident in the dish cultures. It was concluded that the cell-to-cell interaction needed for immune responses to particulate antigens in vitro was more readily interfered with when the cells were spread over a larger surface area. The proliferative response to antigen, as measured by uptake of 3H-thymidine in tube cultures of the sensitive spleen cells, appeared particularly resistant to the depletion effect of adherent cell removal. Dispersed spleen cells from sensitized mice gave a secondary response to sheep erythrocytes. This response was readily abolished by one incubation on absorbent cotton when the cells were cultured in dishes

THYMUS-DERIVED CELL (T CELL) ACTIVATION BY HETEROLOGOUS ANTIGENS AS A REPLACEMENT OF SPECIFIC IMMUNE T CELLS IN THE TRANSFER OF THE SECONDARY RESPONSE TO SHEEP ERYTHROCYTES

Spleen cells from LAF1 mice hyperimmune to sheep erythrocytes (SE) lost their ability to transfer a secondary response to irradiated recipients after incubation with anti-θ and rabbit complement in vitro. Small numbers of specific immune cells even when taken 3 days after a primary SE injection reconstituted the direct and indirect plaque-forming cell responses. Larger numbers of cells sensitized to B. abortus (or keyhole limpet hemocyanin), and given together with the corresponding antigen, also partially reconstituted the ability to respond to SE. This property was mediated by θ-bearing cells and was interpreted as due to a nonspecific humoral factor liberated by specifically activated T cells and acting on B cell proliferation or maturation

Langerhans Cells as Macrophages in Skin and Lymhphoid Organs

Properties of epidermal Langerhans cell were compared with those of a number of other dendritic cells in lymphoid organs and of mononuclear phagocytes. Among the dendritic “reticulum” cells included were indetenninate dendritic cells from the epidermis, inter-digitating “reticulum” cells from T-dependent areas of lymphoid tissue and thymus, follicular dendritic cells of Nossal, and the dendritic cells described by Steinman and Cohn. Luterdigitating cells with typical Birbeck granules, in the thymus and in the paracortices of lymph nodes, which are morphologically indistinguishable from Langerhans cells and indeterminate dendritic cells in the epidermis, appear to belong to the same system and possibly represent a subpopulation of “macrophages.” On the basis of their similarity to these other dendritic cells, we believe Langerhans cells may function in antigen presentation, lymphokine production, provision of a microenvironment for T lymphocytes, and prostaglandin secretion