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

被引:25
作者
Chattopadhyay, Gouri
Khan, Abdul Q.
Sen, Goutam
Colino, Jesus
duBois, Wendy
Rubtsov, Anatoly
Torres, Raul M.
Potter, Michael
Snapper, Clifford M.
机构
[1] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA
[2] Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA
[3] NCI, Genet Lab, Bethesda, MD 20892 USA
[4] Univ Colorado, Hlth Sci Ctr, Denver, CO 80207 USA
[5] Natl Jewish Med & Res Ctr, Integrated Dept Immunol, Denver, CO 80207 USA
关键词
D O I
10.4049/jimmunol.179.11.7523
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 (mlg) 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.
引用
收藏
页码:7523 / 7534
页数:12
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