Helper signals in the plaque-forming cell response to protein-bound haptens.

Abstract

We have been interested in determining the mechanisms by which helper T cells collaborate with B cells in the generation of specific antibody responses. Based on a variety of experimental approaches we have proposed that the induction of B cell IgM plaque-forming cells (PFC) ~ responses to protein-bound haptens requires two types of helper T cell signals, the first both antigen specific and B cell Ia restricted and the second mediated by nonspecific factors, i.e. interleukins (1-6). Studies designed to test the synergistic effects of nonspecific factors and antigen-specific helper T cells have been complicated because the interleukins may have effects on T cell functions as well as, or instead of, the B cell response under study.We previously established the ability of a series ofT cell hybridomas to deliver antigen-specific, B cell Ia-restricted helper signals in the PFC response to soluble protein antigens (5). In addition to the obligate requirement for the antigenspecific helper T cell signal, the elicitation of optimal PFC responses was to varying degrees dependent on the addition of nonspecific factors provided by culture supernatants of concanavalin A-stimulated (Con A SN) spleen cells. This system offers an ideal opportunity to investigate the effects of nonspecific factors on B cell responses to soluble protein antigens under circumstances in which we are confident the effects of the factors are on the B cells themselves and not on the T cell hybridomas.Our primary approach to studying the interleukins involved in the generation of specific B cell antibody responses has been the primary in vitro PFC response to sheep erythrocytes (SRBC). Unlike the antibody response to soluble proteins, spleen Con A SN are sufficient to drive the anti-SRBC PFC response of T celldepleted splenic B cells (6). Using splenic B cells rigorously depleted of T cells and macrophages (MO) we have been able to replace the activity of spleen Con

Heterogeneity of helper/inducer T lymphocytes. II. Effects of interleukin 4- and interleukin 2-producing T cell clones on resting B lymphocytes.

“…These results indicate that Thl cells do not produce the factors necessary for activating resting B lymphocytes, and that neither IL-2 nor IFN -'Y is obligatory for such responses. Such a conclusion contradicts a number of earlier studies showing that IL-2 and IFN-y are important helper factors for B cells (9)(10)(11)(12) . Many of these earlier studies used erythrocytes as antigens (9,12), and it is possible that this represents a unique situation that cannot be extrapolated to soluble proteins .…”

“…Such a conclusion contradicts a number of earlier studies showing that IL-2 and IFN-y are important helper factors for B cells (9)(10)(11)(12) . Many of these earlier studies used erythrocytes as antigens (9,12), and it is possible that this represents a unique situation that cannot be extrapolated to soluble proteins . Moreover, we and others have shown that Thl cells (and their secreted mediators) can help previously activated B cells (23) lated polyclonally in the presence of high concentrations of antigen (4), particularly if the inhibitory effect of IFN-y is neutralized.…”

“…Thus, many cytokines, including IL-1, IL-2, IFN-'y, IL-4, and IL-5, have been shown to influence B cell growth and/or differentiation in vitro (9)(10)(11)(16)(17)(18), but the critical question of which are obligatory for antibody responses to low (physiologic) concentrations of protein antigens is not yet resolved . The recent identification if la-restricted helper T cell subsets that differ in lymphokine secretion profiles, and the development of neutralizing antibodies specific for lymphokines, provide two approaches for addressing this question .…”

Interaction and Activation of Antigen‐Specific T and B Cells

“…Both are released by Thi cells stimulated with antigen-pulsed APC or mitogens (Mosmann et al 1986b). IL-2 can be both a growth and differentiation factor for activated B cells (Liebson et al 1981, Parker 1982, Marrack et al 1982, Brooks & Vitetta 1986) and y-l¥'H has both inhibitory and stimulatory activity on B cells {Roehm et al 1983, OUveret al 1987).…”

B Cell‐Tropic Interleukins in Murine Systemic Lupus Erythematosus (SLE) 1

“…activity (Tl-class I) or by their poiyvalency and ability to crosslink antigen receptors (Tl-class 2) (Snow et al 1983a(Snow et al , 1983b. On the other hand, most antigens are so-called "T dependent" (TD) (e.g., Trinitrophenol-Keyhole limpet hemocyanin) and require both Signal 1 and Signal 2 to induce B cell activation (Roehm et al 1983). Signal 2 consists of a direct antigen-specific, larestricted T cell-B cell interaction (Singer et al 1982).…”