title: CD40 stimulation promotes human secondary immunoglobulin responses in HuPBL-SCID chimeras.
abstract: Antibodies to CD40 have been demonstrated to promote B-cell growth and differentiation in vitro. In order to determine if CD40 stimulation could promote antigen-specific human immunoglobulin (Ig) production in vivo, we examined the effects of anti-human CD40 MoAb in an in vivo system where human peripheral blood lymphocytes (huPBL) were engrafted into mice with severe combined immune deficiency (SCID). The huPBL-SCID mice were then given various doses of diphtheria-tetanus toxoid (DT) vaccine and were examined for the presence of human DT-specific antibodies by ELISA. Surprisingly, treatment with anti-CD40 significantly lowered background DT responses versus untreated chimeras in unimmunized huPBL-SCID mice. However, after immunization, huPBL-SCID mice treated with anti-CD40 MoAb responded to a significantly greater extent in response to the vaccine compared with control huPBL-SCID mice, although total Ig levels were sometimes lower in anti-CD40-treated mice. The predominant Ig isotype induced after immunization was IgG. Thus, CD40 stimulation promotes human secondary IgG responses in huPBL-SCID mice. These data demonstrate that CD40 stimulation is capable of promoting antigen-specific human B-cell responses in vivo.
authors.affiliation: Laboratory of Leukocyte Biology, Division of Basic Sciences, Frederick, Maryland, 21702-1201, USA. murphyw@ncifcrf.gov
authors.forename: W J
authors.initials: WJ
authors.lastname: Murphy
authors.forename: S
authors.initials: S
authors.lastname: Funakoshi
authors.forename: W C
authors.initials: WC
authors.lastname: Fanslow
authors.forename: H C
authors.initials: HC
authors.lastname: Rager
authors.forename: D D
authors.initials: DD
authors.lastname: Taub
authors.forename: D L
authors.initials: DL
authors.lastname: Longo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000494:pharmacology*; D002678:Chimera / Q000276:immunology*; D004168:Diphtheria Toxoid / Q000276:immunology / Q000494:pharmacology; D022422:Diphtheria-Tetanus Vaccine; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005677:G(M1) Ganglioside / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D013745:Tetanus Toxoid / Q000276:immunology / Q000494:pharmacology; D017778:Vaccines, Combined / Q000276:immunology / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D004168:Diphtheria Toxoid; D022422:Diphtheria-Tetanus Vaccine; D000939:Epitopes; D007074:Immunoglobulin G; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside