CpG drives human transitional B cells to terminal differentiation and production of natural antibodies

Federica Capolunghi, Simona Cascioli, Ezio Giorda, Maria Manuela Rosado, Alessandro Plebani, Cinzia Auriti, Giulio Seganti, Roberta Zuntini, Simona Ferrari, Maria Cagliuso, Isabella Quinti, Rita Carsetti

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Abstract

The receptor TLR9, recognizing unmethylated bacterial DNA (CpG), is expressed by B cells and plays a role in the maintenance of serological memory. Little is known about the response of B cells stimulated with CpG alone, without additional cytokines. In this study, we show for the first time the phenotypic modification, changes in gene expression, and functional events downstream to TLR9 stimulation in human B cell subsets. In addition, we demonstrate that upon CpG stimulation, IgM memory B cells differentiate into plasma cells producing IgM Abs directed against the capsular polysaccharides of Streptococcus pneumoniae. This novel finding proves that IgM memory is the B cell compartment responsible for the defense against encapsulated bacteria. We also show that cord blood transitional B cells, corresponding to new bone marrow emigrants, respond to CpG. Upon TLR9 engagement, they de novo express AID and Blimp-1, genes necessary for hypersomatic mutation, class-switch recombination, and plasma cell differentiation and produce Abs with anti-pneumococcal specificity. Transitional B cells, isolated from cord blood, have not been exposed to pneumococcus in vivo. In addition, it is known that Ag binding through the BCR causes apoptotic cell death at this stage of development. Therefore, the ability of transitional B cells to sense bacterial DNA through TLR9 represents a tool to rapidly build up the repertoire of natural Abs necessary for our first-line defense at birth.

Original languageEnglish
Pages (from-to)800-808
Number of pages9
JournalJournal of Immunology
Volume180
Issue number2
Publication statusPublished - Jan 15 2008

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ASJC Scopus subject areas

  • Immunology

Cite this

Capolunghi, F., Cascioli, S., Giorda, E., Rosado, M. M., Plebani, A., Auriti, C., Seganti, G., Zuntini, R., Ferrari, S., Cagliuso, M., Quinti, I., & Carsetti, R. (2008). CpG drives human transitional B cells to terminal differentiation and production of natural antibodies. Journal of Immunology, 180(2), 800-808.