Antibodies play an essential role in defending vertebrates against infectious agents and toxins, but, can also induce or exacerbate disease. To better control antibody production, more needs to be learned about the natural mechanisms that regulate B lymphocyte activation and differentiation. In vitro experiments have delineated stimuli that can lead to B cell activation and/or differentiation. These include 1) the crosslinking of B cell surface (s) Ig by antigen or anti-Ig antibody; 2) stimulatory T cell-derived lymphokines; and 3) direct, antigen-mediated interactions between antigen-specific B and T lymphocytes. Little is known, however, about the relative importance of these stimuli in the generation of in vivo antibody responses. To investigate this matter, a system was developed in which the injection of mice with a goat antibody to IgD activates B cells by crosslinking their sIgD, enhances helper cell expression of a receptor for IgD, induces helper T cells to secrete stimulatory lymphokines, and makes possible direct interactions between goat IgG-specific helper cells and sIgD+ B cells. These events stimulate a large, rapid, T cell-dependent polyclonal IgG response. To study the importance of these events in the generation of a polyclonal IgG response this system has been modified by the use of: 1) monoclonal anti-IgD antibodies that differ in their abilities to crosslink IgD and their abilities to be seen as foreign by T cells in different mouse strains; 2) cell transfers between mice that differ only in their Ig allotypes; and 3) alternate mechanisms for the activation of helper T lymphocytes. Issues to be studied include 1) whether the crosslinking of B cell sIgD contributes to the generation of an Ig response in these mice; 2) if so, whether the crosslinking of B cell sIgD contribute to the generation of an IgG response through a) its direct B cell activating effects b) the induction of enhanced T cell IgD receptor expression, and/or c) enhancement of T cell activation; 3) the extent to which crosslinking of B cell sIgD in the absence of sIgD-mediated interactions between adjacent B cells activates these cells; 4) whether a direct anti-IgD antibody-mediated cellular interaction between B cells and activated helper T cells is required for the induction of a polyclonal antibody response in anti-IgD antibody-injected mice; and 5) whether anti-IgD antibody-induced lymphokines can, in the absence of other stimuli, stimulate B cell DNA synthesis.
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