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

Dextran, of the variety commonly used as plasma expander, markedly altered antibody synthesis to an unrelated antigenic stimulus, SRBC, in two animal species, guinea pig and mouse. The time at which dextran was administered relative to antigen was found to be most critical for increasing or decreasing the number of IgM and IgG PFC. Furthermore, these times differed for the two species studied. Typically, when given to guinea pigs 6 h before SRBC, dextran caused a 20-fold rise in IgM-producing cells but had little effect upon IgG synthesis. However, if dextran preceded antigen by 24 h the same magnitude of increase was seen in IgG-forming cells while a decrease in IgM-producing cells occurred. In mice, a short 2 h interval between dextran and antigen favored cells synthesizing IgG and not those producing IgM. A longer 6 to 24 h lapse between dextran and antigen resulted again in an inverted pattern, i.e., an increase in IgM and a decrease in IgG-producing cells. In both species, if dextran was given 48 h before antigen, synthesis of IgG markedly decreased. At the cellular level dextran activated those B cells already in the vascular compartment. In stimulating the IgM response to SRBC, dextran appears either to substitute for T cells or to amplify the effects of that small number of T cells still present in bone marrow preparations. Dextran-altered mouse B cells synthesized SRBC-specific IgG in the presence of normal T cells at an earlier time than did normal B and T cells. However, dextran was unable to cause blastogenesis in vitro of guinea pig lymph node cells or mouse B, T, and spleen cells. The data suggest at least two effects that T cells exert upon B cells. One is to stimulate more B cells to produce IgM, a function accomplished by endotoxins, PWM, PPD, and the simple polysaccharide dextran. The other is to trigger shifts in synthesis of immunoglobulins M and G. Our observations are compatible with the view that a single cell is capable of synthesizing both of these immunoglobulins and that the stimulating factor for one may cause cessation of the other.

Section: Discussionmentioning

confidence: 99%

Regulation of Immunoglobulin Synthesis by Dextran

Battisto

Pappas

1973

“…This suggestion is premised on the idea that for in vitro responses to type 1 and 2 antigens and to B cell mitogens, including insolubilized anti-Ig, it is not antigen-specific T cells that influence the magnitude of the response but rather T cell-derived lymphokines that are required to enhance B cell responsiveness. B. abortus functions in vitro as a type 1 antigen, but it also has been shown to stimulate antigen-specific T cells in vivo (18). Thus, it is not surprising that in vivo immunization of normal mice with TNP-BA can stimulate responses dependent on carrier-specific T cells as well as factor-dependent responses.…”

Section: Discussionmentioning

confidence: 99%

Establishment of an inbred line of mice that express a synergistic immune defect precluding in vitro responses to type 1 and type 2 antigens, B cell mitogens, and a number of T cell-derived helper factors.

Mond¹,

Norton²,

Paul³

et al. 1983

Introduction of the CBA/N X-linked gene into C3H mice has resulted in the establishment of a new strain of mice that has profound immunologic defects. B cells from these mice show significantly impaired in vitro immune responses to the T cell-independent type 1 antigen trinitrophenyl-Brucella abortus (TNP-BA) as well as markedly reduced proliferative responses to a number of B cell mitogens when compared with the responses of the parental control mice. The in vivo response of such mice to TNP-BA is, however, comparable to that of CBA/N mice. Furthermore, B cells from C3.CBA/N mice are unresponsive to the plaque-forming cell enhancing effects induced by EL4-derived supernatant in the presence of TNP-BA, unlike B cells obtained from CBA/N or C3H/Hen mice whose responsiveness to TNP-BA can be significantly enhanced in the presence of EL4-derived supernatant. The model we have presented to best explain these results suggests that B cells from C3.CBA/N mice can be stimulated only under conditions in which they can interact with carrier-specific T cell help and not under conditions where factor-dependent responses are dominant.

“…Thymus "independent" antigens may stimulate DNA synthesis by B lymphocytes only (8,9) or by both T and B lymphocytes (10, 11), while thymus-dependent antigens typically stimulate DNA synthesis by both T and B cells (12, 13), with the response of the T ceils generally preceding that of the B cells (5,13). While some of this accelerated DNA synthesis reflects the activity of specific clones of lymphocytes with surface receptors for the antigen selected (14-17), much of it also seems to reflect the activity of cells with no intrinsic specificity for the antigen (15,16,(18)(19)(20)(21)(22)(23)(24)(25). These latter cells presumably are responding to mitogenic factor (18, 19), possibly to other T cell products (20-25) and possibly to other substances whose sources are not presently defined.…”

mentioning

confidence: 99%

Selective Dna Synthesis by Cells Specifically Localizing in Response to Xenogeneic Erythrocytes

Thursh

Emeson

1973

One of the basic effects of antigens on lymphocytes is to stimulate DNA synthesis and cell division. This effect is readily demonstrable in vitro (1-3) and in vivo (4-7). Thymus "independent" antigens may stimulate DNA synthesis by B lymphocytes only (8, 9) or by both T and B lymphocytes (10, 11), while thymus-dependent antigens typically stimulate DNA synthesis by both T and B cells (12, 13), with the response of the T ceils generally preceding that of the B cells (5, 13). While some of this accelerated DNA synthesis reflects the activity of specific clones of lymphocytes with surface receptors for the antigen selected (14-17), much of it also seems to reflect the activity of cells with no intrinsic specificity for the antigen (15,16,(18)(19)(20)(21)(22)(23)(24)(25). These latter cells presumably are responding to mitogenic factor (18, 19), possibly to other T cell products (20-25) and possibly to other substances whose sources are not presently defined. This background of nonspecific stimulation has made it very difficult to study the antigen-induced DNA synthesis of specifically reacting cells directly.We have recently described a system whereby it is possible to concentrate recirculating long-lived lymphocytes of a particular specificity by secondary antigenic stimulation (15,16). Unfortunately this secondary stimulation also results in the nonspecific trapping of many other long-lived recirculating lymphocytes in the same lymph nodes (15, 16). The present studies, which were undertaken to try to refine this system, are based on the following two observations: first, most rapidly dividing lymphoid cells do not ordinarily recirculate (26) and therefore have little tendency to accumulate in antigenically stimulated lymph nodes (27, Emeson, Thursh, and Noble, unpublished observation), and, second, cells with specific reactivity for an antigen seem to rapidly synthesize DNA at very specific times after antigenic stimulation (28, 29). It was hoped that labeling cells for a very brief period after antigenic stimulation might make it possible to define conditions where specifically reactive cells were labeling much more rapidly than other recirculating