title: Distinct Mechanisms Underlie Boosted Polysaccharide-Specific IgG Responses Following Secondary Challenge with Intact Gram-Negative versus Gram-Positive Extracellular Bacteria.
abstract: Priming of mice with intact, heat-killed cells of Gram-negative Neisseria meningitidis, capsular serogroup C (MenC) or Gram-positive group B Streptococcus, capsular type III (GBS-III) bacteria resulted in augmented serum polysaccharide (PS)-specific IgG titers following booster immunization. Induction of memory required CD4(+) T cells during primary immunization. We determined whether PS-specific memory for IgG production was contained within the B cell and/or T cell populations, and whether augmented IgG responses following booster immunization were also dependent on CD4(+) T cells. Adoptive transfer of purified B cells from MenC- or GBS-III-primed, but not naive mice resulted in augmented PS-specific IgG responses following booster immunization. Similar responses were observed when cotransferred CD4(+) T cells were from primed or naive mice. Similarly, primary immunization with unencapsulated MenC or GBS-III, to potentially prime CD4(+) T cells, failed to enhance PS-specific IgG responses following booster immunization with their encapsulated isogenic partners. Furthermore, in contrast to GBS-III, depletion of CD4(+) T cells during secondary immunization with MenC or another Gram-negative bacteria, Acinetobacter baumannii, did not inhibit augmented PS-specific IgG booster responses of mice primed with heat-killed cells. Also, in contrast with GBS-III, booster immunization of MenC-primed mice with isolated MenC-PS, a TI Ag, or a conjugate of MenC-PS and tetanus toxoid elicited an augmented PS-specific IgG response similar to booster immunization with intact MenC. These data demonstrate that memory for augmented PS-specific IgG booster responses to Gram-negative and Gram-positive bacteria is contained solely within the B cell compartment, with a differential requirement for CD4(+) T cells for augmented IgG responses following booster immunization.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
authors.forename: Swagata
authors.identifier: 0000-0003-3702-6207
authors.initials: S
authors.lastname: Kar
authors.affiliation: Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
authors.forename: Swadhinya
authors.initials: S
authors.lastname: Arjunaraja
authors.affiliation: Laboratory of Bacterial Polysaccharides, U.S. Food and Drug Administration, Silver Spring, MD 20993; and.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Akkoyunlu
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
authors.forename: Gerald B
authors.identifier: 0000-0002-9112-2331
authors.initials: GB
authors.lastname: Pier
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; clifford.snapper@usuhs.edu.
authors.forename: Clifford M
authors.identifier: 0000-0001-7724-5186
authors.initials: CM
authors.lastname: Snapper
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009345:Neisseria meningitidis / Q000145:classification / Q000276:immunology*; D011134:Polysaccharides / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000145:classification / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D011134:Polysaccharides