Augmented B lymphocyte response to antigen in the absence of antigen-induced B lymphocyte signaling in an IgG-transgenic mouse line.
IgG-containing B cell antigen receptor (IgG-BCR), the BCR mostly expressed on memory B cells, contains a distinct signaling function from IgM-BCR or IgD-BCR expressed on naïve B cells. Because naïve B cells transgenic for IgG exhibit augmented response to antigens similar to memory B cells, the distinct signaling function of IgG-BCR appears to play a role in augmented antibody responses of memory B cells. However, how IgG-BCR signaling augments B cell responses is not yet well understood. Here we demonstrate that B cells from IgG-transgenic mice are anergic with defect in generation of BCR signaling upon BCR ligation. However, these IgG-transgenic B cells generate markedly augmented antibody response to a T cell-dependent antigen, probably due to hyper-responsiveness to a T cell-derived signal through CD40. Both BCR signaling defect and augmented response to CD40 ligation are partially restored in xid IgG-transgenic mice in which BCR signaling is down-modulated due to a loss-of-function mutation in the tyrosine kinase Btk crucial for BCR signaling. Thus, IgG-BCR induces augmented B cell responses in the absence of antigen-induced BCR signaling probably through high ligand-independent BCR signaling that may "idle" B cells to make them ready to respond to T cell help. This finding strongly suggests a crucial role of ligand-independent signaling in receptor function.
Man
Rong-Yong
RY
Laboratory of Immunology, Graduate School of Biomedical Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Onodera
Taishi
T
Komatsu
Emi
E
Tsubata
Takeshi
T
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D015398:Signal Transduction
D000941:Antigens; D007074:Immunoglobulin G; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse