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

Abstract

Inhibition of mitogenic stimulation of mouse I y m phocytes by ant i-mouse i m munogl obu I in antibodies 1. Mode of actionAntibodies with specificities for mouse p-chains and mouse K-and X-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) t o differentiate into immunoglobulin (1g)-secreting, plaque-forming cells (PFC). Antibodies with specificities for mouse y-chains or with Ig-unrelated specificities (anti-ovalbumin, anti-E. coli 0-galactosidase) d o not elicit this inhibition. Bivalent pepsin (Fab')* 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 t o inhibit differentiation into PFC. Rabbit as well as chicken anti-Ig antibodies are inhibitory; this indicates that the inhibition is not complementmediated. 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 t o 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,

Neurocytotoxic antibodies in serum of patients with systemic lupus erythematosus

“…Alternatively, antibodies to cell-membrane antigens that are not part of receptor-combining sites may also prevent cell activation by external stimuli. In vitro studies with animal cells have demonstrated that mitogen-induced B-cell activation is blocked by antibody to immunoglobulin (29), antigen-induced T-cell proliferation is inhibited by antisera to histocompatibility region antigens (30), and the induction of in vitro colony-forming units in bone marrow cells treated with colony stimulating factor can be inhibited by antibody to brain (31 (32).…”

Notch1 engagement by Delta-like-1 promotes differentiation of B lymphocytes to antibody-secreting cells

“…These results suggest that activation of Notch signaling by Dll1 releases an inhibitory signal that otherwise maintains B cells in a nonsecreting blast state. An in vitro assay that reveals late inhibition of ASC differentiation is based on BCR cross-linking concomitant with LPS-mediated stimulation (15). In this assay, ASC inhibition is an ''all-or-nothing'' phenomenon at the single-cell level, dependent on BCR signal strength and BCR ligand concentration and independent of proliferation and Ig secretion rate (16).…”

“…RNA was extracted with TRIzol and reverse-transcribed by using SuperScript II RT and oligo(dT) [12][13][14][15][16][17][18] primer (Life Technologies, Gaithersburg, MD). Primer sequences are listed in SI Table 1.…”

B Cells Expressing a Natural Polyreactive Autoantibody Have a Distinct Phenotype and Are Overrepresented in Immunoglobulin Heavy Chain Transgenic Mice

“…Stimulation with LPS also triggered a proliferation of ppc1-5H/ 1 B cells, but the response was slightly weaker than that of the ppc1-5H/ or non-tg B cells. This may be due to their prior BCR engagement (62).…”