T Cell Replacing Factors in the B Cell Response to Antigen¹

Abstract

The initial studies on T cell replacing factors were carried at a time when the complexity ofthe cell interactions in the B cell response to antigen had yet to be fully appreciated. The requirement for helper T cells was demonstrated by the studies of Claman and his colleagues, and by Mitchell, Miller, and others. The work of Mitchison, Rajewsky and other demonstrated that the T cells were also antigen-specific and that there was a need for "linked recognition". That is to say that the antigen determinants recognized by the T cell had to be physically associated with the antigen determinants recognized by the B cell. This was at first taken as evidence for a need for direct cell-cell interaction between T cell and B cell, but it was soon realized that the same experiments could be accommodated by a model in which T cell help was mediated by small amounts of a locally effective T cell mediator.That the response of T cell-depleted spleens could in fact be restored by T cellderived mediators was first demonstrated in our laboratory (Dutton et al. 1971) and by Schimpl & Wecker (1972). Our experiment made use ofthe observation that large numbers of T cells were activated when MHC-disparate lymphocytes were mixed and showed that mixed lymphocyte reaction (MLR) culture supernatants contained a T cell replacing factor. It was quickly shown that other culture supernatants of concanavalin A (Con A) or antigen-activated T cells contained a similar activity (Andersson et al. 1972).The picture became more complicated when it was shown that such culture supernatants would not replace T cells in all B cell responses. Thus it was shown that histocompatible antigen-specific T cells were required in the response of

CD8 T cell priming by B lymphocytes is CD4 help dependent

“…We show that T cell help for CD8 T cell activation by antigen-presenting B lymphocytes can also be transferred with the supernatant of antigen activated CD4 T cells, a fact reminiscent of experiments in which T cell help for antibody responses in vitro could be replaced by the supernatant of activated CD4 T cells [29], or a combination of IL-2 and IFN-c [30] or IL-4 and IL-5 [31]. While these studies emphasized the role of cytokines secreted by CD4 T cells in helping antibody responses by B lymphocytes, there is no information about a similar helper role of culture supernatants, or individual cytokines, in MHC class I-restricted activation of CD8 T cells by antigen-presenting B lymphocytes.…”

Human CD14hi monocytes and myeloid dendritic cells provide a cell contact–dependent costimulatory signal for early CD40 ligand expression

“…This model, in contrast to the mouse version, also accounts for the IL-2-dependent nature of Tdependent humoral responses in humans, as well as the ability of IL-12 to promote human B-cell activation and antibody production. 14,[59][60][61][62] Although CD40L was originally associated with B-cell activation and differentiation, it was soon recognized that it plays a role in the activation of multiple antigen-presenting cells and also contributes to T-cell differentiation by inducing IL-12. [63][64][65][66] Through its activation of antigen-presenting cells, CD40L participates in a potentially dangerous positive feedback loop for T-cell activation.…”

Production of a B cell growth-promoting activity, (DL)BCGF, from a cloned T cell line and its assay on the BCL1 B cell tumor.

“…In our own studies (18)(19)(20) we have shown that antibody-forming cells were only obtained when both an IL-2-containing supernatant and a TRF-containing supernatant from the long-term alloreactive Dennert line C.C3.11.75 (DL) were present. In this system we measured the IgM response to sheep erythrocytes (SRBC) ofanti-Thy-1 and anti-Lyt-2 plus complement-treated Sephadex G-10-passaged B cells from the spleens of anti-thymocyte serum-(ATS) injected mice.…”

“…We have found that although some IL-2-containing supernatants contained a factor that supported B cell proliferation, this activity did not parallel the activity of these supernatants. However, the TEF activity of these supernatants, as measured in the antibody response assay, did closely parallel the T cell growth factor activity over a 1000-fold range of activity (19,20). For this and other reasons we have concluded that it is IL2 itself rather than another factor present in the IL-2-containing supernatants that is required.…”