Inhibition of lipopolysaccharide-induced activation of immature B cells by anti-mu and anti-delta antibodies and its modulation by interleukin-4.
Soluble anti-Ig or anti-mu antibodies completely abrogate the lipopolysaccharide (LPS)-stimulated proliferation of purified B cells obtained from spleens of 5-7 day old mice. This provides further evidence for the powerful nature of the negative signals transduced by sIgM receptors on immature B cells. In addition, ligation of sIgD receptors (expressed by approximately 30% of these cells) by two out of three monoclonal anti-delta antibodies inhibits the response to LPS by some 50%. Ligation of sIgD on purified sIgD+ B cells (greater than 98% sIgD+) completely inhibited the LPS response of these cells. The inclusion of IL-4 in these cultures partially (with anti-mu), or completely (with anti-delta), restored the proliferative response. Immobilized anti-mu or anti-delta caused comparable levels of inhibition as the soluble antibodies: IL-4 again rescued the inhibition caused by immobilized anti-delta, but not that induced by anti-mu. These results therefore indicate that engaging either sIgM or sIgD receptors on developing B cells delivers negative (tolerogenic) signals. They also implicate IL-4 as a major (although not the only) T cell-derived influence which can modulate these signals. Finally, the data suggest that extensive cross-linking of sIgM (by immobilized anti-mu) causes more profound unresponsiveness in immature B cells, which cannot be rescued by IL-4 alone.
Brines
R D
RD
Laboratory of Cellular Immunology, National Institute for Medical Research, London, UK.
Klaus
G G
GG
D000818:Animals; D000831:Animals, Newborn; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002453:Cell Cycle; D007138:Immunoglobulin delta-Chains; D007148:Immunoglobulin mu-Chains; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D011961:Receptors, Fc / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007138:Immunoglobulin delta-Chains; D007148:Immunoglobulin mu-Chains; D008070:Lipopolysaccharides; D011961:Receptors, Fc; D011971:Receptors, Immunologic; C050855:immunoglobulin D receptor; C035311:immunoglobulin M receptor; D015847:Interleukin-4