Recent findings show that the immune, nervous and endocrine systems develop in parallel and influence each other's function. An interrelationship between these organ systems suggets that an environmental insult to one system may result in a functional alteration in the other. Our studies show that early in vitro exposure of lymphocytes to norepinephrine enhances IgM antibody production via B2-adrenoceptor stimulation. B2-adrenoceptor enhancement induces a twofold increase in the number of resting antigen-specific B lymphocytes that differentiate into antibody-secreting cells without affecting the proliferative capacity of each resting cell that is recruited. B2-agonist pretreatment of B cells, but not resting Th-2 cells, induces an increase in both the frequency of resting B cells that differentiate into anti-TNP IgM-secreting cells and the amount of anti-TNP IgM secreted. Resting B cells, but not resting Th-2 cells, expressed high affinity B2ARs that functionally transduced signals to increase intracellular levels of cAMP. In attempt to confirm the above in vitro findings in vivo, we have desinged an animal model that utilizes a lymphocyte-deficient scid mouse. Our work shows that the scid mouse can be reconstituted with the same enriched populations of antigen-specific T and B lymphocytes used in vitro studies. Also, our results show that these mice secrete antigen-specific antibody after primary and secondary immunization, unless they are pretreated before reconstruction with 6-hydroxydopamine to destroy norepinephrine-containing nerve terminals. These studies have implications for basic biomedical and clinical research on brain-immune interactions. An understanding of integrated system function will contribute to an increasesd understanding of immune and neuroendocrine function, and will contribute to the development of targeted drug strategies to prevent toxicities that may result from exposure of integrated biological system to enviromental factors.
