BACTERIAL LIPOPROTEINS MAY SUBSTITUTE FOR CYTOKINES IN THE HUMORAL IMMUNE-RESPONSE TO T-CELL-INDEPENDENT TYPE-II ANTIGENS

Bacterial lipoproteins share a common structural motif that has been s hown to stimulate proliferation and Ig secretion of murine B cells, in a manner distinct from that mediated by LPSs, Studies of lipoprotein- mediated B cell activation utilized heterogeneous populations of lymph oid cells, leaving unresolved their ability to directly activate resti ng B cells, as well as their ability to interact with other B cell sti muli. Using highly enriched and/or sort-purified resting murine B cell s, we demonstrate that, in contrast to previous reports, lipoproteins (lipoprotein-D, lipoprotein-OspA, and/or the synthetic analogue Pam,Cy s) stimulate little, if any, proliferation or Ig secretion in resting B cells, However, when combined with a multivalent membrane (m)Ig-medi ated cross-linking signal, dextran-conjugated anti-IgD Abs (alpha delt a-dex), lipoproteins mediate up to 10,000-fold inductions in IgM secre tion and up to 25-fold enhancements in cellular proliferation relative to that observed with alpha delta-dex alone, in the absence of added cytokines. This mig-mediated enhancement of Ig secretion was not obser ved when B cells were stimulated with bivalent, unconjugated anti-Ig. CD40 ligand (CD40L), shows a similar, although somewhat more moderate, synergy with lipoproteins for induction of proliferation and IgM secr etion, By contrast, lipoproteins by themselves are relatively ineffect ive at costimulating Ig secretion in the presence of various combinati ons of cytokines. These data suggest that bacteria may induce Ag-speci fic humoral immunity through the action of bacterial polysaccharides t hat mediate an Ag-specific multivalent mig signal, in concert with bac terial lipoproteins that deliver ancillary signals, without a requirem ent for recruitment of non-B cell types.