title: Transgenic expression of Bcl-xL or Bcl-2 by murine B cells enhances the in vivo antipolysaccharide, but not antiprotein, response to intact Streptococcus pneumoniae.
abstract: IgG antipolysaccharide (PS) and antiprotein responses to Streptococcus pneumoniae (Pn) are both CD4(+) T cell dependent. However, the primary IgG anti-PS response terminates more quickly, uses a shorter period of T cell help, fails to generate memory, and is more dependent on membrane Ig (mIg) signaling. We thus determined whether this limited anti-PS response to Pn reflected a greater propensity of PS-specific B cells to undergo apoptosis. We used mice that constitutively expressed the antiapoptotic protein Bcl-x(L) or Bcl-2 as a B cell-specific transgene. Both transgenic (Tg) mice exhibited increased absolute numbers of splenic B-1 and peritoneal B-1b and B-2 cells, subsets implicated in anti-PS responses, but not in marginal zone B (MZB) cells. Both Tg mouse strains elicited, in an apparently Fas-independent manner, a more prolonged and higher peak primary IgM and IgG anti-PS, but not antiprotein, response to Pn, but without PS-specific memory. A similar effect was not observed using purified PS or pneumococcal conjugate vaccine. In vitro, both splenic MZB and follicular Tg B cells synthesized DNA at markedly higher levels than their wild-type counterparts, following mIg cross-linking. This was associated with increased clonal expansion and decreased apoptosis. Using Lsc(-/-) mice, the Pn-induced IgG response specific for the capsular PS was found to be almost entirely dependent on MZB cells. Collectively, these data suggest that apoptosis may limit mIg-dependent clonal expansion of PS-specific B cells during a primary immune response to an intact bacterium, as well as decrease the pool of PS-responding B cell subsets.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Gouri
authors.initials: G
authors.lastname: Chattopadhyay
authors.forename: Abdul Q
authors.initials: AQ
authors.lastname: Khan
authors.forename: Goutam
authors.initials: G
authors.lastname: Sen
authors.forename: Jesus
authors.initials: J
authors.lastname: Colino
authors.forename: Wendy
authors.initials: W
authors.lastname: DuBois
authors.forename: Anatoly
authors.initials: A
authors.lastname: Rubtsov
authors.forename: Raul M
authors.initials: RM
authors.lastname: Torres
authors.forename: Michael
authors.initials: M
authors.lastname: Potter
authors.forename: Clifford M
authors.initials: CM
authors.lastname: Snapper
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D051020:bcl-X Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C494812:Bcl2l1 protein, mouse; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D004247:DNA