Evidence for the inactivation of precursor B cells in high dose unresponsiveness

Abstract

THE mechanisms of tolerance induction, a state of specific antigen induced unresponsiveness in lymphocytes, are still ill understood. The impetus to generate information on these mechanisms derives from the practical importance of understanding “self-tolerance”. Both T (thymus-derived) and B (bone marrow-derived) lymphocytes can be rendered specifically unresponsive to antigen. This paper examines the nature of the unresponsiveness induced in B cells by high doses of two types of antigen; firstly by a set of hapten conjugates known to be thymus-independent tntigens (DNP-SIII, DNP-Levan, DNP-Dextran)¹ and secondly by a known thymus-dependent conjugate (TNP-BSA). It is now well authenticated that for efficient antibody production B cells need to proliferate after which members of the proliferated clone may differentiate into antibody producers. It is therefore important to establish whether unresponsiveness induced in B cells occurs by inactivation of the precursor cell or by an effect on the derived clone. We here demonstrate that in vitro, B cell unresponsiveness induced by both kinds of antigens (thymus-dependent and independent) results solely from the inactivation of the precursor hapten specific B cells, so that these cells cannot expand into normal antibody producing clones, rather than by any mechanism which may have affected the clone size such precursor cells could yield.