The pattern of joining (JH) gene usage in the human IgH chain is established predominantly at the B precursor cell stage.
Preferential utilization of JH and D genes has been demonstrated in the rearranged IgH chain in human peripheral B cells. We report here that the same hierarchy of JH gene usage is observed in leukemic cells arrested in the B precursor stage of differentiation. Specifically, JH4 and JH6 accounted for 42.9% and 35.7%, respectively, of the JH gene usage in the leukemias compared with an expected frequency of 16.7% assuming unbiased gene usage. Within the D gene families, the DN1 gene appears to be overutilized in both populations, representing about 15% of the total gene usage compared with an expected frequency of 3.2%. Because 21 of the 36 leukemias contained only nonproductive IgH rearrangements, the preferential gene usage could not have arisen from pre-B cells that have undergone clonal selection after a productive rearrangement but before surface Ig expression. Nonproductive rearrangements exhibited the biased gene usage seen for productive rearrangements. These findings suggest that a recombination bias favoring certain segments may be the actual mechanism responsible for the apparent preferential utilization of JH and D genes.
Wasserman
R
R
Division of Oncology, Children's Hospital of Philadelphia, PA 19104.
Ito
Y
Y
Galili
N
N
Yamada
M
M
Reichard
B A
BA
Shane
S
S
Lange
B
B
Rovera
G
G
D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007223:Infant; D008969:Molecular Sequence Data
D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region