title: B cell intrinsic MyD88 signals drive IFN-gamma production from T cells and control switching to IgG2c.
abstract: 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-gamma 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.
authors: Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom. tom.barr@ed.ac.uk
authors: Tom A
authors: TA
authors: Barr
authors: Sheila
authors: S
authors: Brown
authors: Pietro
authors: P
authors: Mastroeni
authors: David
authors: D
authors: Gray
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D007074:Immunoglobulin G; D053594:Myeloid Differentiation Factor 88; D007371:Interferon-gamma