title: Human Ig production and isotype switching in severe combined immunodeficient-human mice.
abstract: Severe combined immunodeficient (SCID) mice were transplanted with different human fetal organs (SCID-hu mice), including thymus, liver, spleen, and omentum, and the serum levels of human IgM, IgG, IgE, and IgA were measured. In all SCID-hu mice significant levels (up to 590 ng/ml) of IgM were detected, irrespective of the organs transplanted. In contrast, IgG was present (up to 530 ng/ml) only when the fetal thymus was transplanted together with the fetal liver, indicating that the presence of human T cell is a prerequisite for in vivo isotypes switching by human B cells in SCID-hu mice. Additional transplantation of fetal spleen did not significantly increase IgG levels. was observed 4 months after transplantation. At that time, analysis by IEF showed that human IgG present in SCID-hu serum was at least oligoclonal. Furthermore, all IgG subclasses were represented in the human IgG pool. Human B cells were undetectable in the peripheral blood, spleen, and bone marrow of these SCID-hu mice; in contrast, B cells expressing CD19 could be isolated from the SCID-hu thymus. Considerable proportions of the CD19+ B cells coexpressed CD5, CD7, CD10, CD40, and CD2. These B cells spontaneously produced IgM and IgG in vitro and could be induced to switch to IgE-producing cells when cocultured with cloned activated CD4+ T cells in the presence of IL-4. Collectively, these data demonstrate that functionally mature B cells able to produce IgM and IgG in vivo, and IgE in vitro, are present in the SCID-hu human thymus.
authors.affiliation: DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304-1104.
authors.forename: B A
authors.initials: BA
authors.lastname: Vandekerckhove
authors.forename: D
authors.initials: D
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Punnonen
authors.forename: D
authors.initials: D
authors.lastname: Schols
authors.forename: H C
authors.initials: HC
authors.lastname: Lin
authors.forename: B
authors.initials: B
authors.lastname: Duncan
authors.forename: R
authors.initials: R
authors.lastname: Bacchetta
authors.forename: J E
authors.initials: JE
authors.lastname: de Vries
authors.forename: M G
authors.initials: MG
authors.lastname: Roncarolo
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D002678:Chimera; D002999:Clone Cells; D016332:Fetal Tissue Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000166:cytology; D051379:Mice; D016513:Mice, SCID; D013950:Thymus Gland / Q000166:cytology
chemical_list: D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M