Impaired CD40-signalling in CD19-deficient mice selectively affects Th2-dependent isotype switching.
Activation of B lymphocytes involves binding of antigen to the specific receptor and signalling through several membrane coreceptors, of which CD19 has been found to play a pivotal role as a response regulator. Although previous studies in CD19 gene knockout mice have demonstrated that antibody responses to T-cell-dependent antigens are strongly impaired in the absence of this coreceptor, little is known about the consequences of CD19 deficiency for the interaction between T and B cells. Here we report that Th2 co-ordinated B-cell differentiation is selectively impaired in CD19-deficient mice in response to mucosal or systemic immunizations or following an intestinal infection with Nippostrongylus brasiliensis. Whereas immunoglobulin (Ig)G1 or IgE antibody responses were low or absent, IgG2a responses were normal. The selective defect was not caused by a poor Th2-development or interleukin (IL)-4 responsiveness in CD19-deficient mice. Rather, it was the result of an impaired Th2-B cell interaction, owing to a substantially reduced ability to signal via CD40 in CD19-deficient B cells. Thus, our study in CD19-deficient mice suggests that CD40L-CD40-interactions are more important for Th2 than for Th1 co-ordinated B-cell differentiation.
Gärdby
E
E
Department of Medical Microbiology and Immunology, University of Göteborg, S-413 46 Göteborg, Sweden.
Chen
X J
XJ
Lycke
N Y
NY
D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000534:Alum Compounds; D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002772:Cholera Toxin / Q000276:immunology; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D007114:Immunization / Q000379:methods; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D007073:Immunoglobulin E / Q000172:deficiency; D007074:Immunoglobulin G / Q000097:blood; D007274:Injections, Intraperitoneal; D015847:Interleukin-4 / Q000494:pharmacology; D007411:Intestinal Diseases, Parasitic / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology; D008211:Lymphocyte Cooperation / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology; D019948:Receptors, Interleukin-4 / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D017206:Strongylida Infections / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D018941:Antigens, CD19; D019013:CD40 Antigens; D007074:Immunoglobulin G; D019948:Receptors, Interleukin-4; D023201:CD40 Ligand; D015847:Interleukin-4; C041524:aluminum sulfate; D007073:Immunoglobulin E; D002772:Cholera Toxin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin