Polyclonal activation of the murine immune system by an antibody to IgD. III. Ontogeny

Abstract

It has recently been demonstrated that the injection of adult mice with an affinity-purified goat antibody to mouse IgD (GaM delta) stimulates activation of the humoral immune system that resembles, on a polyclonal level, specific B cell activation by a T cell-dependent antigen. One to 2 days after adult BALB/c mice are injected with 200 micrograms of GaM delta, their splenic B lymphocytes undergo a series of T-independent activation steps that include increases in surface (s) Ia expression, cell size and DNA synthesis. Seven days after GaM delta injection, these cells undergo T-dependent activation steps, that include further proliferation as well as differentiation into IgG1-secreting cells. We have now studied the ontogeny of the T-independent (day 2) and T-dependent (day 7) activation steps by injecting 100-200 micrograms of GaM delta into 3-day- to 10-week-old BALB/c mice. GaM delta failed to induce increases in B cell sIa expression or size 2 days after injection of mice 2 weeks old or younger and failed to stimulate increased DNA synthesis 2 days after injection of 4-week-old mice. In contrast, increases in spleen cell sIa expression, size and DNA synthesis were seen 7 days after injection of 6- to 8-day-old mice. Furthermore, increases in the numbers of spleen cells with large amounts of intracytoplasmic IgG1 were seen at the same time, although these increases were much less than were seen in GaM delta-treated adult mice. Thus, the ability of GaM delta to induce T help and to act in concert with such help to stimulate B cell proliferation and differentiation precedes in ontogeny the ability of GaM delta to directly induce B cell proliferation and early differentiative events. In addition, the early activating events that we have studied are not required for T-dependent B cell proliferation and antibody production to occur, although they appear to contribute to the magnitude of clonal expansion and antibody production.