The ontogeny of B lymphocytes. III. Opposite signals transmitted to B lymphocyte precursor cells by inducing agents and hormones

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Abstract
Present evidence supports the idea that agents inducing phenotype conversion in B and T precursor cells can be obtained from many sources (e.g. LPS, cate‐cholamines, prostaglandin E1, and DB cyclic AMP). They share the feature of raising intracellular cyclic AMP in some systems. Our experiments have demonstrated another class of components (carbamyl choline, insulin, human growth hormone, 8‐bromo‐cyclic GMP) which inhibit induction of phenotype conversion in early B lymphocyte precursor cells. All of these substances are known or suspected to raise levels of intracellular cyclic GMP. The blocking effect is transient as precursor cells regain inducibility after removal of the inhibitor within 2 to 4 h. Thymopoietin (TP), which is a selective inducing agent for conversion of prothymocytes (Thy‐1 −) to thymocytes (Thy‐1+), inhibited the induction of expression of B cell markers, Ig and Ia. Conversely, tumor necrotizing serum (TNS), which selectively induces B precursor cells (Ig− → Ig+ and Ia− → Ia+), inhibited the inducing effect of TP on prothymocytes. We propose that induction requires interaction of a specific inducing hormone with a receptor associated with adenylate cyclase, whereas inhibition of induction requires interaction with a receptor which activates guanylate cyclase. Our data indicate that prothymocytes and pro‐B cells have receptors for both TP and TNS, which are, however, associated with different signal mechanisms in B and T precursor cells. The manner in which a given precursor cell responds depends less on the specificity of hormone receptor interaction than on pre‐set receptor associations to deliver stop or go signals. This system can be regarded as a model for regulation of T and B cell differentiation by pairs of hormones with opposing effects.