Aberrations of the B-cell receptor B29 (CD79b) gene in chronic lymphocytic leukemia.
Leukemic B cells in chronic lymphocytic leukemia (B-CLL) typically exhibit low or undetectable surface Ig. Because the B29 (CD79b and Ig beta) and mb-1 (CD79a and Ig alpha) gene products are required for surface Ig display in the B-cell receptor complex (BCR), we analyzed the expression of these genes in B-CLL cells. The majority (83%) of the randomly selected B-CLL patient samples analyzed exhibited low or undetectable surface BCR measured by mu heavy chain and B29 expression. Levels of mb-1 mRNA in these B-CLL samples with low surface BCR were similar to those in normal B cells. Among those with decreased surface expression, B29 mRNA was not detected in half of these B-CLL samples. The remaining B-CLL samples with diminished surface BCR contained normal levels of B29 mRNA. Further analysis of cDNA clones from the majority of these latter samples contained point mutations, insertions, or deletions that were largely located in the B29 transmembrane and cytoplasmic domains. These results indicate the occurrence of somatic mutations predicted to affect B29 expression and/or function in the majority of B-CLL and suggest that these aberrations underlie the diminished surface BCR display and loss of BCR signaling characteristic of this leukemia.
Thompson
A A
AA
Department of Pediatrics, UCLA School of Medicine and The Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA.
Talley
J A
JA
Do
H N
HN
Kagan
H L
HL
Kunkel
L
L
Berenson
J
J
Cooper
M D
MD
Saxon
A
A
Wall
R
R
D015703:Antigens, CD / Q000032:analysis / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D051925:CD79 Antigens; D002469:Cell Separation; D002869:Chromosome Aberrations; D003001:Cloning, Molecular; D005434:Flow Cytometry; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000032:analysis; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000032:analysis / Q000235:genetics
D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; D007148:Immunoglobulin mu-Chains; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell