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Slc15a4 function is required for intact class switch recombination to IgG2c in response to TLR9 stimulation
Author(s) -
Dosenovic Pia,
Ádori Monika,
Adams William C,
Pedersen Gabriel K,
Soldemo Martina,
Beutler Bruce,
Karlsson Hedestam Gunilla B
Publication year - 2015
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2014.82
Subject(s) - isotype , immunoglobulin class switching , stimulation , in vivo , immunology , biology , immune system , tlr9 , antibody , microbiology and biotechnology , b cell , gene , endocrinology , genetics , gene expression , monoclonal antibody , dna methylation
Signalling through Toll‐like receptors (TLRs) by endogenous components of viruses or bacteria can promote antibody (Ab) isotype switching to IgG2a/c. Multiple cell types are capable of responding to TLR stimulation in vivo and the processes underlying TLR‐induced Ab isotype switching are not fully defined. Here, we used feeble mice, which are deficient in the peptide/histidine transporter solute carrier family 15 member 4 (Slc15a4), and fail to produce cytokines including interferon alpha (IFNα) in response to TLR9 stimulation, to study Ab isotype switching to IgG2c in response to vaccination. We demonstrate that the production of IgG2c in response to CpGA‐adjuvanted vaccines was severely reduced in feeble mice, while a more subtle defect was observed for CpGB. The reduced IgG2c production in feeble could not be ascribed to defective plasmacytoid dendritic cell (pDC) responses alone as we found that splenic cDCs and B cells from feeble mice were also defective in response to TLR9 ligation ex vivo . We conclude that Slc15a4 is required for intact function of TLR9‐expressing cells and for effective Ab isotype switching to IgG2c in response to CpG‐adjuvanted vaccines.