Cross-linking of lymphocytic surface immunoglobulin inhibits its production via a cyclic nucleotide mechanism

Abstract

When antibody to immunoglobulin (anti-Ig) reacts with Ig molecules on B-lymphocyte surfaces the Ig, tethered by the antibody, moves over the surface to form patches and finally a cap at one pole of the cell. Simultaneously, the Ig–antibody complexes are removed by pinocytosis at the patches and cap, until the surface is cleared of the target molecules^1,2. In immunofluorescent studies, Sidman and Unanue³ followed the reappearance of the surface Ig during subsequent culture of the cells. They observed that splenic lymphocytes from adult mice re-express surface Ig promptly, whereas those from neonatal animals re-express poorly or not at all. They suggested that this phenomenon might be related to the greater susceptibility of lymphocytes from immature animals to tolerisation by antigen. Such an interpretation was supported by a simultaneous study⁴ showing that explanted mouse fetal lymphocytes were less able to re-express surface Ig after treatment by anti-Ig than were adult lymphocytes. However, Ault and Unanue⁵ later reported in man a similar dichotomy between blood and nodal lymphocytes, the former re-expressing surface Ig more poorly. We report here studies on guinea pig leukaemic lymphocytes, which have also shown delayed re-expression of surface Ig after clearing by antibody. We present evidence that the delayed re-expression reflects a reduction in the normal delivery rate associated with turnover at the surface. The reduction follows a train of events initiated by cross-linking of the surface Ig and including an increase in intracellular cyclic AMP. Furthermore, the shutdown in delivery is apparently specific, inasmuch as delivery of two other surface molecules we have been able to quantify proceeds unimpeded. These observations suggest a basic mechanism expressed to varying extents by normal lymphoid populations to account for their differing rates of surface Ig regeneration^3–5.