IL-7-dependent B lymphocytes are essential for the anti-polysaccharide response and protective immunity to Streptococcus pneumoniae.
Young children are impaired in their response to T cell-independent (TI) Ags, such as pneumococcal polysaccharide (PPS). B lymphopoeisis early in life is IL-7 independent, whereas in adults it is IL-7 dependent. Therefore, we hypothesized that IL-7-driven B lymphopoiesis plays a critical role in promoting Ab responses to TI Ags. Young but not adult mice are impaired in responses to PPS vaccination and to 4-hydroxy-3-nitrophenyl-acetyl-Ficoll, a widely studied model TI Ag, and B1b cells generate Ab responses to these Ags. In this paper, we show that, despite having B1b, B1a, and MZ B cells-all of which are involved in TI responses-young wild-type or adult mice deficient either in IL-7 or in IL-7Ralpha are severely impaired in anti-PPS responses and do not survive Streptococcus pneumoniae challenge, indicating IL-7-dependent B cells are required for TI immunity. Consistent with this, PPS immunization induced a robust TI response in young IL-7 transgenic mice that was comparable to adult wild-type responses. Moreover, immunized young or adult IL-7 transgenic mice were completely resistant to S. pneumoniae challenge. Our data indicate that activating the IL-7 signaling pathway could restore impaired TI responses in the young.
Shriner
Anne K
AK
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Liu
Hongqi
H
Sun
Guizhi
G
Guimond
Martin
M
Alugupalli
Kishore R
KR
D000375:Aging / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000955:Antigens, T-Independent / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D007075:Immunoglobulin M / Q000096:biosynthesis; D015851:Interleukin-7 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011008:Pneumococcal Infections / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D000955:Antigens, T-Independent; D007075:Immunoglobulin M; D015851:Interleukin-7; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial