Low dose unresponsiveness with a thymus independent antigen

Abstract

LIPOPOLYSACCHARIDES (LPS) from Gram-negative bacteria are very efficient carriers for haptenic determinants, so that B cells can be activated by such conjugates to produce antihapten responses both in vivo and in vitro in the absence of T helper cells^1–3 and macrophages (our unpublished data). Trinitrophenylated LPS (TNP–LPS) is one such thymus-independent antigen. Most antigens of this category can induce unresponsiveness in animals only when administered in high concentrations⁴, unlike certain thymus-dependent antigens which can induce unresponsiveness in vivo in both low doses (low zone unresponsiveness) and high doses (high zone unresponsiveness)⁵. In the case of low zone unresponsiveness to thymus-dependent antigens, only helper T-cell functions seem to be affected⁶. It was therefore interesting when we observed that very low doses of LPS could render mice unresponsive to subsequent TNP coupled to LPS. Only in one previous case has low zone unresponsiveness to a thymus-independent antigen been observed, and this was with pneumococcal polysaccharide (SSS III) through a mechanism involving suppressor T cells⁷. We report here that low zone unresponsiveness achieved with LPS is highly specific and requires no obvious T-cell-mediated suppressor mechanisms, thus indicating a further type of regulation mechanism for antibody responses. As LPS are intimately related to other bacterial surface antigens it may be that similar mechanisms operate in the determination of natural immunological reactions against Gram-negative bacteria.