Relatively normal human lymphopoiesis but rapid turnover of newly formed B cells in transplanted nonobese diabetic/SCID mice.
Human B lineage lymphocyte precursors in chimeric nonobese diabetic/SCID mice transplanted with umbilical cord blood cells were directly compared with those present in normal bone marrow. All precursor subsets were represented and in nearly normal proportions. Cell cycle activity and population dynamics were investigated by staining for the Ki-67 nuclear Ag as well as by incorporation experiments using 5-bromo-2'-deoxyuridine. Again, this revealed that human B lymphopoiesis in chimeras parallels that in normal marrow with respect to replication and progression through the lineage. Moreover, sequencing of Ig gene rearrangement products showed that a diverse repertoire of V(H) genes was utilized by the newly formed lymphocytes but there was no evidence for somatic hypermutation. The newly formed B cells frequently acquired the CD5 Ag and had a short life span in the periphery. Thus, all molecular requirements for normal B lymphocyte formation are present in nonobese diabetic/SCID mice, but additional factors are needed for recruitment of B cells into a fully mature, long-lived pool. The model can now be exploited to learn about species restricted and conserved environmental cues for human B lymphocyte production.
Rossi
M I
MI
Immunobiology and Cancer Program, Molecular Immunogenetics, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Medina
K L
KL
Garrett
K
K
Kolar
G
G
Comp
P C
PC
Shultz
L D
LD
Capra
J D
JD
Wilson
P
P
Schipul
A
A
Kincade
P W
PW
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D018956:CD5 Antigens / Q000032:analysis; D002453:Cell Cycle; D019070:Cell Lineage; D016922:Cellular Senescence; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006085:Graft Survival; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D011828:Radiation Chimera; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016511:Severe Combined Immunodeficiency / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013047:Specific Pathogen-Free Organisms; D014183:Transplantation, Heterologous
D000944:Antigens, Differentiation, B-Lymphocyte; D018956:CD5 Antigens; D007135:Immunoglobulin Variable Region