Major histocompatibility complex controls clonal proliferation of CD5+ B cells in H-2-congenic New Zealand mice: a model for B cell chronic lymphocytic leukemia and autoimmune disease.
By employing H-2-congenic NZB, NZW and (NZB x NZW)F1 mice with either the homozygous H-2d/H-2d, H-2z/H-2z or heterozygous H-2d/H-2z haplotype, we found that in the spleen of all the congenic strains homozygous for H-2z, there were extremely high frequencies of CD5+ B cells. These cells eventually proliferated in an oligoclonal or even monoclonal fashion, and B cell-chronic lymphocytic leukemia (B-CLL) developed in some cases. Because this feature was not observed in H-2d/H-2d homozygotes or H-2d/H-2z heterozygotes, the high CD5+ B cell frequencies are apparently controlled by the homozygosity of a locus or cluster of loci closely linked to H-2z complex of NZW strain. As the CD5+ B cell frequencies in the peritoneal cavity did not differ among the H-2-congenic strains, the frequencies of these cells in the peritoneal cavity and in the spleen appear to be at least in part under separate control. Flow cytometry and Southern blot analyses using an immunoglobulin gene JH probe revealed that the H-2z/H-2z homozygotes, there was a propagation of distinct clonal populations between the spleen and the peritoneal cavity, a finding which suggested that in the major histocompatibility complex (MHC)-related microenvironments for CD5+ B cell propagation differ between the two compartments. All our findings taken together imply that certain different but related MHC haplotypes may predispose either to B-CLL or to autoimmune disease, in close relatives.
Okada
T
T
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Takiura
F
F
Tokushige
K
K
Nozawa
S
S
Kiyosawa
T
T
Nakauchi
H
H
Hirose
S
S
Shirai
T
T
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000950:Antigens, Ly / Q000276:immunology; D001327:Autoimmune Diseases / Q000473:pathology*; D016175:B-Lymphocyte Subsets / Q000166:cytology*; D018956:CD5 Antigens; D002999:Clone Cells; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics; D006239:Haplotypes; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D010529:Peritoneal Cavity / Q000166:cytology; D013154:Spleen / Q000166:cytology
D015703:Antigens, CD; D000950:Antigens, Ly; D018956:CD5 Antigens; D006183:H-2 Antigens