Ly-1 B-cell clones similar to human chronic lymphocytic leukemias routinely develop in older normal mice and young autoimmune (New Zealand Black-related) animals.
Studies presented here demonstrate that individually expanded clones of murine Ly-1 B cells, perhaps analogous to the expanded neoplastic Leu-1 B-cell clones in human chronic lymphocytic leukemias, are universally detectable in young New Zealand Black (NZB)-related autoimmune mice and in senescent normal mice (greater than 18 months old). These clones are visible as phenotypically homogeneous cell populations in multiparameter fluorescence-activated cell sorter analyses of peritoneal and splenic B cells; they show unique immunoglobulin heavy- and light-chain gene rearrangements in Southern gel analyses of peritoneal and splenic DNA; and, like the self-replenishing Ly-1 B-cell population from which they are drawn, they tend to grow readily in irradiated or unirradiated syngeneic or allotype congenic hosts. Furthermore, they develop and generalize in primary and secondary hosts in a characteristic pattern (peritoneum much greater than spleen greater than lymph node greater than bone marrow) that suggests that their initial growth is controlled by the mechanisms that normally control Ly-1 B-cell distribution in lymphoid organs. The universal emergence of these clones within the Ly-1 B-cell lineage may be explained by the substantially greater opportunity for hyperplastic and neoplastic transformation events in this long-lived self-replenishing Ly-1 B-cell population, which must divide relatively frequently to maintain its normal size throughout adulthood. Repeated exposure to internal or environmental antigens (with which Ly-1 B cells are known to react) may also play a role in driving the development of these clones.
Stall
A M
AM
Department of Genetics, Stanford University, CA 94305.
Fariñas
M C
MC
Tarlinton
D M
DM
Lalor
P A
PA
Herzenberg
L A
LA
Strober
S
S
Herzenberg
L A
LA
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D000950:Antigens, Ly / Q000032:analysis*; D001402:B-Lymphocytes / Q000032:analysis*; D002999:Clone Cells / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010537:Peritoneum / Q000166:cytology; D010641:Phenotype
D000943:Antigens, Differentiation; D000950:Antigens, Ly