The Ability of Bacterial Lipopolysaccharide to Modulate the Induction of Unresponsiveness to a State of Immunity

Abstract

There exists a body of evidence which details that the antibody response to a number of different antigens requires the cooperation between thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) in a reaction whose net effect is the production of specific antibody by B cells (1). Both of these lymphocyte classes can be made specifically unresponsive to a given antigen (2), although each specific population displays a distinct kinetic pattern in the induction and maintenance of unresponsiveness (3).Bacterial lipopolysaccharides (LPS) 1 are mitogenic for B lymphocytes (4, 5), a phenomenon which may be related to their ability to circumvent the requirement of T cells for antibody formation to antigens which normally require cellular cooperation. The latter has been demonstrated both in vivo or in vitro using such T celldependent antigens as sheep erythrocytes (6-8), haptens (9, 10), and serum proteins (11). LPS can also prevent immunological unresponsiveness. This effect was originally described by Claman (12), who observed that mice which were given LPS after a normally tolerogenic dose of bovine gamma globulin (BGG) did not become tolerant. Golub and Weigle (13) subsequently defined the temporal relationship between the injection of tolerogen and LPS and furthermore demonstrated that the effect of LPS on the induction of tolerance was independent of its activity on the phagocytic index of the reticuloendothelial system.

Immunologic properties of bacterial lipopolysaccharide (LPS). III. Genetic linkage between the in vitro mitogenic and in vivo adjuvant properties of LPS.

“…In this case, analysis of a larger number of mice may reveal recombinants between these two LPS properties. Nonetheless, it should be stressed that a normal complement of antigen-specific T cells is not necessary for the effect of LPS on HGG tolerance, since LPS appears to have no influence on the induction of tolerance to HGG in specific T cells (1,6).…”

The in vitro induction of immunological tolerance in the B lymphocyte by oligovalent thymus-dependent antigens.

“…Additionally, the mechanism is likely to differ in the case of thymus-dependent and thymus-independent antigens since the latter substances in fact nonspecifically abrogate B-cell tolerance induction by the former (7,8). Questions particularly suited to an in vitro analysis of tolerance induction in splenic B cells concern the proposal of Diener and Feldmann (9) that a multivalent presentation of antigen is an obligatory requirement for tolerance induction in the B cell, and also the kinetics of tolerance induction in a defined pool of B cells that is not being altered by the B-cell neogenesis that occurs in the bone marrow (10) .…”

Modulation of Immune Response by Bacterial Lipopolysaccharide (LPS): Roles of Macrophages and T Cells in In Vitro Adjuvant Effect of LPS on Antibody Response to T Cell‐Dependent and T Cell‐Independent Antigens

“…The enhancing effect (adjuvant effect) of LPS has been thought to be caused by direct activation of B cells by LPS; LPS induces DNA synthesis (15) and polyclonal antibody production by B cells (15,17), and it enhances specific antibody response in circumstances where effects of helper T cells are absent or limited (16,20,28). LPS also prevents induction of immunological tolerance in B cells (12). On the basis of these effects of LPS on B cell responses, some investigators (12,28) have postulated that LPS acts directly on B cells as a second signal in the framework of a two-signal model of immunity (2).…”

“…LPS also prevents induction of immunological tolerance in B cells (12). On the basis of these effects of LPS on B cell responses, some investigators (12,28) have postulated that LPS acts directly on B cells as a second signal in the framework of a two-signal model of immunity (2). However, this interpretation should be reconsidered in view of reports showing that T cells or macrophages are involved as essential cellular elements in the adjuvant effect of LPS.…”