Neisserial porins may provide critical second signals to polysaccharide-activated murine B cells for induction of immunoglobulin secretion

Abstract

Resting B cells stimulated with dextran-conjugated anti-immunoglobulin D (anti-IgD) antibodies (anti-Igdex), 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 elucidate the parameters which costimulate T-cellindependent antipolysaccharide antibody responses during bacterial infections, we tested the capacities of highly purified porin proteins from Neisseria meningitidis and Neisseria gonorrhoeae to augment in vitro proliferation and induce Ig secretion by anti-Ig-dex-activated B cells. Resting B cells, from lipopolysaccharide (LPS)-nonresponsive C3H/HeJ mice, proliferated and secreted 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 proliferation and Ig secretion. Similar synergistic effects of porins with CD40-ligand were also observed. These effects of porins were shown to occur directly at the level of the B cell. The predominant Ig isotype elicited in response to porins plus anti-Ig-dex or CD40-ligand was IgM (>97%), with the remainder comprising IgG. Surprisingly, picogram-per-milliliter amounts of neisserial LPS were also found to be highly synergistic with anti-Ig-dex for induction of IgM secretion by LPS-responsive C3H/HeN, but not C3H/HeJ, B cells. Thus, these data suggest that porins, as well as LPS, may provide critical second signals for T-cell-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. These data may also help to explain the potent immunopotentiating effects of porins for polysaccharidespecific, as well as protein-specific, humoral responses in vivo.

B‐cell activation by T‐cell‐independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms

“…These proteins, which serve as molecular sieves on the surfaces of a number of gram-negative bacteria such as Neisseria meningitidis and Salmonella typhimurium (120), can stimulate B-cell expression of co-stimulatory B7.2 molecules, proliferation and Ig secretion (121,122). We have observed synergy between ad-dex and three purified neisserial porins in IgM induction that was similar to the synergy of ad-dex with LPS, but did not require TLR4 expression (117).…”

Bactericidal antibody response to Neisseria meningitidis serogroup B in patients with bacterial meningitis: effect of immunization with an outer membrane protein vaccine

“…B7-2 is involved in costimulation during B cell^T cell interactions. A subsequent study demonstrated a synergistic e¡ect of neisserial porins with CD40 ligand which is expressed in activated T cells [10]. Taken together, these data suggest a physiological role for porins in augmenting T cell participation on the immune response to Neisseria.…”

B‐cell subsets and the mature ­preimmune repertoire. Marginal zone and B1 B cells as part of a “natural immune memory”

“…This NK T-cell expansion occurs within a similar time frame to the MZ-derived plasmablast wave. The expansions of both cell types may be induced by non-protein components of bacteria cell walls, such as Gram-negative-derived mitogens including LPS as well as newly described mitogens from Grampositive bacteria and glycolipids presented by CD1 (84)(85)(86).…”