A Murine Model for Analysis of Spontaneous Induction and Feedback Regulation of Specific Antibody Synthesis

A mouse model system has been developed in which antibody specific for human serum albumin (HSA) was produced spontaneously in irradiated recipients of lymph node cells. This response occurred in the absence of exogenous HSA when draining lymph node cells from mice immunized months earlier were adoptively transferred. This spontaneous response was inhibited by administration of rabbit anti-HSA indicating that rabbit antibody can mediate feedback suppression in the mouse. Transfer of non-draining lymph node cells or spleen cells, even from the same mice, resulted in insignificant spontaneous induction of anti-HSA. The antibody levels in recipients of draining lymph node cells increased with time up to 15 days after adoptive transfer and were directly proportional to the number of cells transferred. Incubation of donor cells in vitro was not required for spontaneous induction but generally enhanced spontaneous responses in recipients. Secondary immunization of the donor mice also enhanced the response. We attribute this spontaneous induction of antibody synthesis to antigen persisting in the draining lymph nodes. It appears that persisting antigen may play a major role in the maintenance and regulation of serum antibody levels. This mouse system is amenable to both in vitro and in vivo manipulations. This flexibility makes it an attractive model for studying the role of persisting antigen and other factors responsible for the maintenance and regulation of serum antibody.