Search

As perhaps the staunchest advocates of repertoire purging as the central mechanism of immunological tolerance, we note with satisfaction a spate of recent, elegant papers which suggest an intrathymic clonal abortion model as the explanation for at least some examples of T-cell tolerance. This view agrees with the classical formulation of the Billingham-Brent-Medawar school of tolerance as a specific, central failure of immune responsiveness. Repertoire purging within the B-lymphocyte compartment remains much more controversial. There is no doubt that experimental models exist where the B cell is the reversible target of tolerance induction. The question is, in view of the ease of inducing autoantibody formation both in vivo and in vitro, just how relevant are such clonal anergy mechanisms to authentic self-tolerance? Arguments are presented that there must be two windows of tolerance susceptibility in the ontogeny of the B cell; one while it is maturing in the bone marrow, to prevent autoreactivity of high affinity to important accessible self-antigens; and a second soon after activation of pre-memory cells by exogenous antigen, to prevent fortuitous mutations towards high-affinity anti-self-reactivity establishing a forbidden clone. [ABSTRACT FROM AUTHOR]

The enhancement effect of some antigens on in vitro colony formation by normal mouse bone marrow cells is mediated through a normal serum αmacroglobulin (αM) which is present in newborn animals and shows no immunological specificity. The proportion of antigen and αM affects colony enhancement, and it has also been shown that specific antibody successfully competes with αM for the antigen. It seems likely that antigen-αM complex acts directly on the colony forming cell, rather than indirectly through release of colony stimulating factor. The possible relevance of this phenomenon to immune induction and, to the effect of antigens in promoting irradiation survival is discussed. [ABSTRACT FROM AUTHOR]

Initiation of an immune response to sheep erythrocytes by the transplantation of spleen cells into irradiated recipients is thought to involve an interaction between two functionally different lymphoid cells. If such populations actually exist, it should be possible to separate them from each other and to study the properties of each type of cell. To this end, mouse spleen cells have been fractionated using equilibrium centrifugation in density gradients of Ficoll. Two functionally different populations of spleen cells were obtained. Neither population was active in initiating an immune response by itself on transplantation into irradiated mice, but mixtures of the two populations were. One population of spleen cells was also active when transplanted together with normal mouse bone marrow and the other population was active when mixed with thymus cells from normal mice. These results indicate that two different spleen cells must interact to initiate an immune response in vivo. The specificity of the cell that synergizes with thymus ceils was investigated further and shown to have antigen-specific receptors on its surface. These cells can be recognized by their ability to make rosettes with erythrocyte antigens. Thus, the ‘background’ rosette-forming cells found in unimmunized mice are actually progenitors of antibody-producing cells. [ABSTRACT FROM AUTHOR]

It has been shown that intraperitoneal injection of Freund's complete adjuvant can stimulate the multiplication and effect the distribution within the animal of cells which form granulocytic and monocytic colonies in vitro. This response is associated with a leukocytosis and a fall in haematocrit. A variety of antigens were tested all of which resulted in an increase in the number of colony forming cells in the spleen to a greater or lesser degree. Two mechanisms are thought to be involved in this response: (1) with some antigens a direct stimulation of colony forming cells by an antigen-α-macroglobulin complex; and (2) an indirect stimulation of colony forming cells by release of colony stimulating factor from cells other than the colony forming cells. [ABSTRACT FROM AUTHOR]

The incorporation of some antigens such as bacterial endotoxin, heterologous erythrocytes and bacterial flagellin preparations can enhance the formation of colonies in cultures of normal mouse bone marrow or foetal liver cells in vitro. Other antigens such as foreign serum proteins and haemocyanin are inactive. This effect depends on the reaction of antigen with a component of normal mouse serum. [ABSTRACT FROM AUTHOR]