title: Limited B cell repertoire in severe combined immunodeficient mice engrafted with peripheral blood mononuclear cells derived from immunodeficient or normal humans.
abstract: The ability to engraft human PBMC or fetal tissue immune cells in the severe combined immunodeficient (SCID) mouse has created a need for characterization of these systems and their application to disease models. We demonstrate that SCID mice reconstituted with PBMC support the growth and differentiation of a restricted set of B cells. Human IgG levels of 1-2 mg/ml (10-20% of normal human serum levels) were routinely achieved in spite of a serum half life of only 12 d. Ig levels peaked around 50 d and Ig production was maintained for greater than 100 d. The Ig was greater than 85% IgG though some IgM, IgA, IgD, and even IgE could be detected. However, the human IgG produced in hu-PBL-SCID mice was pauci-clonal when analyzed by isoelectric focusing and by kappa/lambda light chain usage. Using a new polymerase chain reaction based analysis capable of monitoring individual VH family utilization, we found that the engrafted B cells showed skewed and restricted human VH subfamily utilization. These parameters were markedly variable among hu-PBL-SCID mice reconstituted from the same donor cell population at both early (21-50 d) and late stages (greater than 100 d). Hu-PBL/CVI-SCID mice constructed with cells from patients with common variable immunodeficiency with an in vitro block in terminal B cell differentiation produced human Ig responses that were quantitatively the same as those produced by hu-PBL-SCID mice from normal donors. The hu-PBL-SCID system using PBMC appears to lead to growth and Ig production by a small number of B cells and results in a restricted B cell repertoire.
authors.affiliation: Division of Clinical Immunology and Allergy, UCLA Medical School 90024-1680.
authors.forename: A
authors.initials: A
authors.lastname: Saxon
authors.forename: E
authors.initials: E
authors.lastname: Macy
authors.forename: K
authors.initials: K
authors.lastname: Denis
authors.forename: M
authors.initials: M
authors.lastname: Tary-Lehmann
authors.forename: O
authors.initials: O
authors.lastname: Witte
authors.forename: J
authors.initials: J
authors.lastname: Braun
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007525:Isoelectric Focusing; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012016:Reference Values
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015345:Oligonucleotide Probes