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This Article Full Text (PDF) All Versions of this Article: jimmunol.0803706v1 183/2/1005    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Barr, T. A. Articles by Gray, D. PubMed PubMed Citation Articles by Barr, T. A. Articles by Gray, D.

B Cell Intrinsic MyD88 Signals Drive IFN- Production from T Cells and Control Switching to IgG2c

Tom A. Barr^*, Sheila Brown^*, Pietro Mastroeni and David Gray^*

^*Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; and Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom

The question of whether Ab responses to T-dependent Ags require B cell intrinsic signaling via the main TLR adaptor (MyD88) has become embroiled in confusion. In part this may be related to the methods used to analyze B cell intrinsic signaling. We have used a mixed bone marrow chimera model to generate mice in which the B cell compartment is completely deficient in MyD88 expression, while the other hematopoietic lineages are largely normal. These mice were immunized with T-dependent Ags or infected with Salmonella. We found that the Ag-specific IgG2c primary response was absolutely dependent on MyD88 signaling to B cells, while other Ig classes were not (IgG1 and IgG3) or much less so (IgG2b, IgA). The MyD88^B–/– chimeric mice exhibited an impairment of development of IFN- effector T cells, a likely contributory factor in the lack of IgG2c. We also found that B cell intrinsic MyD88 signals are required for the production of natural Abs. The data emphasize the nonredundant role of B cells as programmers of T cell differentiation in vivo.

Address correspondence and reprint requests to Dr. Tom Barr and Dr. David Gray, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Ashworth Laboratories, King’s Buildings, West Mains Road, Edinburgh, EH9 3JT U.K. E-mail addresses: tom.barr{at}ed.ac.uk and d.gray{at}ed.ac.uk