title: Signals from activation of B-cell receptor with anti-IgD can override the stimulatory effects of excess BAFF on mature B cells in vivo.
abstract: The selection and maturation of B-cell clones are critically determined by tonic signals from activated B cell receptors (BCR) and survival signals from BAFF cytokine. These finely tuned and coordinated signals provide a net positive signal that can promote the selection, maturation, proliferation and differentiation of a developing B cell. Stimulation with an anti-IgD antibody can also activate BCR but can lead to depletion and an arrest of mature B-cell development in vivo. It is not known whether survival signals from excess BAFF can override the suppressive effects of treatment with anti-IgD on mature B cells in vivo. Herein, we examined the effects of co-treatment of BAFF and anti-IgD on the mature B-cell compartment and antibody production in vivo by treating mice with either 1mg/kg BAFF or anti-IgD alone or in combination for 3 consecutive days. We found that co-treatment with anti-IgD significantly abrogated these stimulatory effects of BAFF treatment on splenic CD19+ B cells as well as mature CD19+IgD(hi)IgM+ B cells in vivo. Anti-IgD down-regulated the expression of the BCR complex (mIgM, mIgD and CD19) and the BAFF receptor TACI without regard to the presence of BAFF. Anti-IgD treatment also significantly negated BAFF-induced IgM production in vivo. Both BAFF and anti-IgD could individually stimulate IL-10 synthesis in B cells but did not affect one another. Taken together, our data suggest that activation of BCR with an anti-IgD antibody can override the stimulatory effects from excess BAFF on B cell proliferation and antibody production by down-regulating the expression of BCR complex and BAFF receptors.
authors: Autoimmunity and Immunotherapy Research, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; Perinatal Research, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. Electronic address: tgnguyen@med.usyd.edu.au.
authors: Tue G
authors: TG
authors: Nguyen
authors: Perinatal Research, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; Northern Clinical School, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065 Australia.
authors: Jonathan M
authors: JM
authors: Morris
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000494:pharmacology; D018941:Antigens, CD19 / Q000378:metabolism; D053264:B-Cell Activating Factor / Q000494:pharmacology*; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013154:Spleen / Q000166:cytology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D018941:Antigens, CD19; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; C039951:anti-IgD; D016753:Interleukin-10
keywords: Anti-IgD; Anti-IgM; Autoimmune; B-cell maturation; B-cell receptor; BAFF receptor