NEISSERIAL PORINS MAY PROVIDE CRITICAL 2ND SIGNALS TO POLYSACCHARIDE-ACTIVATED MURINE B-CELLS FOR INDUCTION OF IMMUNOGLOBULIN SECRETION

Resting B cells stimulated with dextran-conjugated anti-immunoglobulin D (anti-IgD) antibodies (anti-Ig-dex), a model for B-cell activation in response to polysaccharide antigens, proliferate but secrete little if any Ig, unless additional stimuli are present, In order to elucida te the parameters which costimulate T-cell-independent antipolysacchar ide antibody responses during bacterial infections, we tested the capa cities of highly purified porin proteins from Neisseria meningitidis a nd Neisseria gonorrhoeae to augment in vitro proliferation and induce Ig secretion by anti-Ig-dex-activated B cells, Resting B cells, from l ipopolysaccharide (LPS)-nonresponsive C3H/HeJ mice, proliferated and s ecreted IgM in response to each of three distinct porins acting alone, Further, porins, even at concentrations that were minimally inductive when acting alone, were strongly synergistic with anti-Ig-dex for pro liferation and Ig secretion, Similar synergistic effects of porins wit h CD40-ligand were also observed, These effects of porins were shown t o occur directly at the level of the B cell. The predominant Ig isotyp e elicited in response to porins plus anti-Ig-dex or CD40-ligand was I gM (>97%), with the remainder comprising IgG, Surprisingly, picogram-p er-milliliter amounts of neisserial LPS were also found to he highly s ynergistic with anti-Ig-dex for induction of IgM secretion by LPS-resp onsive C3H/HeN, but not C3H/HeJ, B cells, Thus, these data suggest tha t porins, as well as LPS, may provide critical second signals for T-ce ll-independent induction of polysaccharide-specific Ig in response to neisserial and other gramnegative porin-expressing bacterial pathogens , without a requirement for the participation of non-B cell types, The se data may also help to explain the potent immunopotentiating effects of porins for polysaccharide-specific,as well as protein-specific, hu moral responses in vivo.