CpG oligodeoxynucleotides overcome the unresponsiveness of neonatal B cells to stimulation with the thymus-independent stimuli anti-IgM and TNP-Ficoll.
Neonates are very vulnerable to pathogenic encapsulated bacteria due to their inability to mount an antibody response to capsular polysaccharides, which are thymus-independent type 2 (TI-2) antigens (Ag). Oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides induced neonatal B cells to proliferate to anti-IgM, a TI-2 stimulus. CpG ODN inhibited the spontaneous and B cell receptor-mediated apoptosis of neonatal B cells and reduced the amount of the pro-apoptotic Bcl-xS, strongly correlated with anti-IgM-induced apoptosis of neonatal B cells. CpG ODN protected neonatal B cells from apoptosis by down-regulation of the Bcl-xS protein. Neonatal B cells underwent polyclonal differentiation upon stimulation with CpG ODN, but unlike in adult B cells, this was not preceded by IL-6 secretion. CpG ODN stimulated neonatal B cells to mount an Ag-specific antibody response to TNP-Ficoll, another TI-2 Ag. Thus CpG ODN could provide a novel approach to induce the immune system in neonates to respond to harmful encapsulated bacteria.
Chelvarajan
R L
RL
Department of Microbiology and Immunology and Sanders-Brown Research Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA.
Raithatha
R
R
Venkataraman
C
C
Kaul
R
R
Han
S S
SS
Robertson
D A
DA
Bondada
S
S
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000941:Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D003432:Cross-Linking Reagents / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005362:Ficoll / Q000031:analogs & derivatives* / Q000276:immunology; D006241:Haptens / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D014301:Trinitrobenzenes / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D003432:Cross-Linking Reagents; D006241:Haptens; D007075:Immunoglobulin M; D015850:Interleukin-6; D009841:Oligonucleotides; D011947:Receptors, Antigen, B-Cell; C020529:TNP-ficoll; D014301:Trinitrobenzenes; C044203:anti-IgM; D018664:Interleukin-12; D005362:Ficoll; D007371:Interferon-gamma