Inhibition of mitogenic stimulation of mouse lymphocytes by anti‐mouse immunoglobulin antibodies. I. Mode of action

Abstract

Abstract Antibodies with specificities for mouse μ‐chains and mouse ϰ‐ and λ‐chains inhibit the stimulation of the major fraction of splenic lymphocytes from nude mice by lipopolysaccharide (LPS), by the purified protein derivative of tuberculin (PPD) and by fetal calf serum (FCS) to differentiate into immunoglobulin (Ig)‐secreting, plaque‐forming cells (PFC). Antibodies with specificities for mouse γ‐chains of with Ig‐unrelated specificities (anti‐ovalbumin, anti‐ E. coli β‐galactosidase) do not elicit this inhibition. Bivalent pepsin (Fab') 2 fragments mediate the same inhibition at the same concentrations, while monovalent papain Fab fragments of such anti‐Ig antibodies have a 100‐fold lower capacity to inhibit differentiation into PFC. Rabbit as well as chicken anti‐Ig antibodies are inhibitory; this indicates that the inhibition is not complement‐mediated. Cells stimulated for 6 h by LPS can no longer be inhibited by anti‐Ig antibodies from differentiating to PFC, a finding which indicates that changes take place in the mitogen‐stimulated cells which may involve surface‐bound Ig molecules. Inhibition can be abrogated, but only prior to the addition of mitogen to the cells, by proteolytic treatment of the cells or by dissociation of the anti‐Ig antibodies in excess medium with time from the cells. Inhibition of DNA synthesis by anti‐Ig antibodies in splenic lymphocytes is more complex and will be described in a subsequent publication.