Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins

George F. Widhopf, Laura Z. Rassenti, Traci L. Toy, John G. Gribben, William G. Wierda, Thomas J. Kipps

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

We examined the immunoglobulin (Ig) heavy chain variable region genes (VH genes) used by leukemia cells of 1220 unrelated patients with chronic lymphocytic leukemia (CLL). We found 1188 (97%) expressed Ig encoded by a single Ig VH subgroup, the most common of which was VH3 (571 or 48.1%), followed by VH1 (319 or 26.8%) and VH4 (241 or 20.2%). Using allele-specific primers, we found 13.8% of all samples (n = 164) used one major VH1-69 allele, designated 51p1, 163 of which were not somatically mutated. For these cases, there was marked restriction in the structure of the Ig third complementarity determining regions (CDR3s), which were encoded by a small number of unmutated D and JH gene segments. Strikingly, 15 of the 163 cases had virtually identical CDR3s encoded by the second reading frame of D3-16 and JH3. Further analysis revealed that each of these 15 samples used the same unmutated Ig kappa light-chain gene, namely A27. These data reveal that approximately 1.3% (15/1220) of all patients had leukemia cells that expressed virtually identical Ig. This finding provides compelling evidence that the Ig expressed by CLL B cells are highly selected and not representative of the Ig expressed by naive B cells.

Original languageEnglish (US)
Pages (from-to)2499-2504
Number of pages6
JournalBlood
Volume104
Issue number8
DOIs
StatePublished - Oct 15 2004

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B-Cell Chronic Lymphocytic Leukemia
Immunoglobulins
Cells
Genes
Leukemia
Immunoglobulin Light Chain Genes
Immunoglobulin kappa-Chains
Alleles
Complementarity Determining Regions
Reading Frames
Immunoglobulin Heavy Chains
B-Lymphocytes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins. / Widhopf, George F.; Rassenti, Laura Z.; Toy, Traci L.; Gribben, John G.; Wierda, William G.; Kipps, Thomas J.

In: Blood, Vol. 104, No. 8, 15.10.2004, p. 2499-2504.

Research output: Contribution to journalArticle

Widhopf, George F. ; Rassenti, Laura Z. ; Toy, Traci L. ; Gribben, John G. ; Wierda, William G. ; Kipps, Thomas J. / Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins. In: Blood. 2004 ; Vol. 104, No. 8. pp. 2499-2504.
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abstract = "We examined the immunoglobulin (Ig) heavy chain variable region genes (VH genes) used by leukemia cells of 1220 unrelated patients with chronic lymphocytic leukemia (CLL). We found 1188 (97{\%}) expressed Ig encoded by a single Ig VH subgroup, the most common of which was VH3 (571 or 48.1{\%}), followed by VH1 (319 or 26.8{\%}) and VH4 (241 or 20.2{\%}). Using allele-specific primers, we found 13.8{\%} of all samples (n = 164) used one major VH1-69 allele, designated 51p1, 163 of which were not somatically mutated. For these cases, there was marked restriction in the structure of the Ig third complementarity determining regions (CDR3s), which were encoded by a small number of unmutated D and JH gene segments. Strikingly, 15 of the 163 cases had virtually identical CDR3s encoded by the second reading frame of D3-16 and JH3. Further analysis revealed that each of these 15 samples used the same unmutated Ig kappa light-chain gene, namely A27. These data reveal that approximately 1.3{\%} (15/1220) of all patients had leukemia cells that expressed virtually identical Ig. This finding provides compelling evidence that the Ig expressed by CLL B cells are highly selected and not representative of the Ig expressed by naive B cells.",
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