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Bursin is a tripeptide (lysyl-histidyl-glycyl-amide) found in follicular and dendritic reticular epithelial cells of the avian bursa of Fabricius that selectively induces the differentiation of committed B-lymphocyte precursor cells but not of committed T-lymphocyte precursor cells. We now show, in immunoassays with tissue extracts, that bursin is also present in avian and bovine bone marrow. There was, however, a categorical difference between avian liver (bursin-negative) and bovine liver (bursin-positive). Bursin was therefore isolated from bovine liver and bone marrow and the structure of mammalian bursin was determined; it was identical to avian bursin. Immunohistochemical examination of bovine liver showed the presence of bursin within epithelial cells of the intrahepatic bile ducts. These cells have previously been suspected of having an endocrine function because of the rich periductal capillary plexus, which coalesces to form a portal system draining into the liver sinusoids. These findings suggest that bone marrow is a site of bursin production and associated B-cell differentiation in both birds and mammals. The bursin-containing cells of the intrahepatic bile ducts are not associated with developing B cells and it would appear that mammals have evolved a local hepatic function for bursin.

Thymopoietin, a polypeptide hormone of the thymus that has pleiotropic actions on the immune, endocrine, and nervous systems, potently interacts with the neuromuscular nicotinic acetylcholine receptor. Thymopoietin binds to the nicotinic alpha-bungarotoxin (alpha-BGT) receptor in muscle and, like alpha-BGT, inhibits cholinergic transmission at this site. Evidence is given that radiolabeled thymopoietin similarly binds to a nicotinic alpha-BGT-binding site within the brain and does so with the characteristics of a specific receptor ligand. Thus specific binding to neuronal membranes was saturable, of high affinity (Kd = 8 nM), linear with increased tissue concentration, and readily reversible; half-time was approximately 5 min for association and 10 min for dissociation. Binding of 125I-labeled thymopoietin was displaced not only by unlabeled thymopoietin but also by alpha-BGT and the nicotinic receptor ligands d-tubocurarine and nicotine; various other receptor ligands (muscarinic, adrenergic, and dopaminergic) did not affect binding of 125I-labeled thymopoietin. Thymopoietin was shown by ELISA to be present in brain extracts, displacement curves of thymus and brain extracts being parallel to the standard thymopoietin curve, and Western (immuno) blot identified in brain and thymus extracts a thymopoietin-immunoreactive polypeptide of the same molecular mass as purified thymopoietin polypeptide. We conclude that thymopoietin and thymopoietin-binding sites are present within the brain and that the receptor for thymopoietin is the previously identified nicotinic alpha-BGT-binding site of neuronal tissue.