AbstractIt has recently been demonstrated that the injection of adult mice with an affinitypurified goat antibody to mouse IgD (GaMδ) 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 μg of GaMδ, 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 GaMδ 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 μg of GaMδ into 3‐day‐ to 10‐week‐old BALB/c mice. GaMδ 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 7days after injection of 6‐ to 8‐day‐old mice. Furthermore, increases in the numbers of spleen cells with large amounts of intracytoplasmic IgG1were seen at the same time, although these increases were much less than were seen in GaMδ‐treated adult mice. Thus, the ability of GaMδ 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 GaMδ 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, althougt they appear to contribute to the magnitud