Role of Macrophages in Immunological Maturation

Abstract

Recent evidence has suggested that the initiation of antibody synthesis is a two-step process. The first step involves antigen phagocytosis and processing by macrophages (1, 2) and the second step appears to consist of the transfer of immunogenic information from the macrophage to the immunocompetent cell with subsequent initiation of antibody synthesis (3).In most instances immunological immaturity in young or immunological deficiency in adult animals is attributed to the absence of immunocompetent cells. Recently however, it was reported by Gallily and Feldman (4) that the immunological deficiency after low doses of X-irradiation could be restored by the administration of macrophages. This suggests that the immunological insult in adult mice by low doses of X-irradiation is not directed against the immunocompetent (antibody-synthesizing) cell but is directed against the antigen-recognizing or antigen-processing cells, namely the macrophages.In this paper we present evidence suggesting that immunological immaturity in newborn mice is not due to the lack of antibody-synthesizing (immunocompetent) cells but is due, at least in part, to the lack of antigen-recognizing or antigen-processing cells, in the form of competent macrophages. This evidence was obtained by transplanting adult macrophages into newborn mice and finding that this enhanced the rate of immunological maturation to sheep red blood cell antigens. Materials and MethodsAdult C3H/He mice were purchased from the Jackson Memorial Laboratory, Bar Harbor, Me. Newborn mice were obtained from our own colony of C3H/He mice which were originally acquired from the Jackson Memorial Laboratory and maintained by brother and sister matings. Skin grafts can be freely exchanged between our C3H mice and the C3H/He mice obtained from Bar Harbor. All mice were housed in humidified, air-conditioned rooms. They were fed a Purina diet, fortified with occasional portions of dried milk and oats.Treatment of Mavrophage DoTwrs--Peritoneal macrophages were provoked in adult mice by intraperitoneal injection of 3-ml sterile thioglycoUate medium. The thioglycollate (Difco Laboratories, Detroit, Mich.) was prepared by adding 2.98 g powder to 100-ml cold distilled water and dissolved by heating to boiling point.

Cells Involved in the Immune Response

“…eluate) cells (we have observed that approximately 10-20% of the irradiated rabbits die if they are not protected with bone marrow) and (b) to provide the recipient with macrophages and/or other cell types which, although not the predominant cell(s) required for the induction of the primary immune response, may nevertheless be necessary in small numbers in order to potentiate the immune response, or to function in a synergistic fashion. Macrophages have been shown to play an active role in promulgating the sequential steps leading to humoral antibody formation, especially in the primary response (11)(12)(13)(14)(15). It has also been demonstrated that macrophages are retained by the glass bead columns (16)(17)(18) and apparently are not eluted by the procedure utilized in this investigation.…”

Maturation of Hemolysin-Producing Cell Clones

“…However, l:l ratios of total PFC to plaques in the culture dish do occur when nonadherent cells are cultured, thus indicating that PPFC have maturated, but due to a lack of some property contained in the adherent cell population have failed to produce hemolysin-producing progeny. The enhancement of immunocompetence of neonatal mice to SRBC antigens by injecting them with large numbers of adult macrophages has also been reported (20). Macrophages, therefore, are probably a component of the precursor unit.…”

Failure of suckling to transfer immunity to a syngeneic rat sarcoma

“…The Table shows that the growth of tumours in weanling rats from the immunized or the non-immunized (control) This experiment failed to demonstrate in a syngeneic tumour system the effects described by Beer et al (1975) of adoptive transfer of systemic immunity to allografts in sucklings by lymphocytes in the milk. This negative finding could be due either to the failure of such allergized lymphocytes to gain access to the milk or to the inability of the ingested lymphocytes to be absorbed intact.…”

“…BILLINGHAM and his colleagues (Beer et al, 1975;Parmely et al, 1976;Head et al, 1977;Parmely et al, 1977) found that in all species studied, including man and rat, viable lymphocytes and macrophages are normal components of colostrum and milk, and are present in concentrations similar to those found in peripheral blood. The lymphocytes were shown to be capable of acting as responder or stimulator cells in mixed lymphocyte cultures.…”

“…The lymphocytes were shown to be capable of acting as responder or stimulator cells in mixed lymphocyte cultures. While milk leucocytes probably fulfil an important local protective function within the mammary exosecretion, Beer et al (1975) andHead et al (1977) further reported that milk from allogeneic foster mothers influenced the neonate's subsequent immune responses to skin grafts. These authors hypothesized that ingested lymplhocytes become systematized in the recipient because they are able to escape from the lumen of the gastro-intestinal tract, as peptic activity in the neonate only becomes demonstrable 15 days after birth.…”